Penicillium copticola 天然产物分离提取 生物活性

Postharvest fruits are highly susceptible to infections by Penicillium species, particularly Penicillium expansum, P. italicum, and P. digitatum. These infections accelerate fruit spoilage and drive the biosynthesis of hazardous secondary metabolites, including mycotoxins that threaten food safety. However, current understanding of the secondary metabolite profiles, toxicity mechanisms, and detection and detoxification methods of key mycotoxins from fruit-pathogenic Penicillium species is still limited. Through systematic literature analysis, this study catalogs 74 secondary metabolites from these Penicillium species, emphasizing patulin, ochratoxin A, and citrinin as priority mycotoxins. Toxicological evaluations reveal their severe health impacts, including multi-organ toxicity and carcinogenicity. The paper further assesses advanced detection techniques and detoxification strategies, proposing an integrated framework for mycotoxin monitoring and mitigation. By elucidating metabolite profiles, toxicity mechanisms, and intervention strategies, this work enhances the understanding of the metabolic diversity of fruit-pathogenic Penicillium species, strengthens mycotoxin surveillance networks, and supports improved fruit quality and safety control.

Marine-derived Penicillium spp., including Penicillium citrinum, Penicillium chrysogenum, and Penicillium sclerotiorum, have emerged as prolific producers of structurally diverse secondary metabolites with cytotoxic activity. This review systematically categorizes 177 bioactive compounds isolated from marine Penicillium spp. between 2018 and 2024, derived from diverse marine environments such as sediments, animals, plants, and mangroves. These compounds, classified into polyketides, alkaloids, terpenoids, and steroids, exhibit a wide range of cytotoxic activities. Their potency is categorized as potent (<1 μM or <0.5 μg/mL), notable (1–10 μM or 0.5–5 μg/mL), moderate (10–30 μM or 5–15 μg/mL), mild (30–50 μM or 15–25 μg/mL), and negligible (>50 μM or >25 μg/mL). The current review highlights the promising role of marine Penicillium spp. as a rich repository for the discovery of anticancer agents and the advancement of marine-inspired drug development.

In order to investigate bioactive natural products derived from the endophytic fungus Penicillium ochrochloron SWUKD4.1850, a comprehensive study focusing on secondary metabolites was conducted. This research led to the isolation of twenty distinct compounds, including a novel nortriterpenoid (compound 20), alongside nineteen compounds that had been previously characterized (compounds 1–19). The chemical structures of these compounds were elucidated using spectroscopic techniques and nuclear magnetic resonance (NMR) analyses. Compounds 1–17 were isolated for the first time as metabolites of P. ochrochloron. Except for compounds 1–14, significant structural similarity was discerned between the metabolites of the endophytic fungus and those of the host plant. Compound 20 is noted as the inaugural instance of a naturally occurring 27-nor-3,4-secocycloartane schinortriterpenoid, while compound 17 was identified in fungi for the first time. An antifungal assay showed that compound 10 displayed a broader antifungal spectrum and a stronger inhibitory effect towards four important plant pathogens, at inhibitory rates of 74.9 to 85.3%. The in vitro radical scavenging activities of compounds 1, 3, 8, 15, and 16 showed higher antioxidant activity than vitamin C. Moreover, a cytotoxic assay revealed that compound 20 had moderate cytotoxicity against the HL-60, SMMC-7721, and MCF-7 cell lines (IC50 6.5–17.8 μM). Collectively, these findings indicate that P. ochrochloron has abundant secondary metabolite synthesis ability in microbial metabolism and that these metabolites have good biological activity and have the potential to enhance plant disease resistance.

This review article presents an in-depth characterization of the genus Penicillium, a major group of filamentous fungal species known for their biological diversity and ecological impact. Methods for the identification of the various Penicillium species combine macroscopic, microscopic and molecular approaches, as well as phylogenetic analysis. In a first part, the ecology of the Penicillium species, their distribution in various habitats and their key role in ecosystems are presented. Particular emphasis is then placed on Penicillium's ability to produce secondary metabolites with a wide variety of biological and pharmacological properties, including anti-microbial molecules, antioxidants, anti-inflammatory, anti-diabetic, anti-cancer and anti-viral compounds. Because these metabolites are of major interest in biotechnology and pharmaceutical industry, further research and development based on the yet untapped therapeutical and economical potential of this fungal genus should be promoted.

Mangrove ecosystems have attracted widespread attention because of their high salinity, muddy or sandy soil, and low pH, as well as being partly anoxic and periodically soaked by tides. Mangrove plants, soil, or sediment-derived fungi, especially the Penicillium species, possess unique metabolic pathways to produce secondary metabolites with novel structures and potent biological activities. This paper reviews the structural diversity and biological activity of secondary metabolites isolated from mangrove ecosystem-derived Penicillium species over the past 5 years (January 2020–October 2024), and 417 natural products (including 170 new compounds, among which 32 new compounds were separated under the guidance of molecular networking and the OSMAC approach) are described. The structures were divided into six major categories, including alkaloids, polyketides, terpenoids, benzene derivatives, steroids, and other classes. Among these natural products, the plausible biosynthetic pathways of 37 compounds were also proposed; 11 compounds have novel skeleton structures, and 26 compounds contain halogen atoms. A total of 126 compounds showed biological activities, such as cytotoxic, antifungal, antibacterial, anti-inflammatory, and α-glucosidase-inhibitory activities, and 11 compounds exhibited diverse biological activities. These new secondary metabolites with novel structures and potent bioactivities will continue to guide the separation or synthesis of structurally novel and biologically active compounds and will offer leading compounds for the development and innovation of pharmaceuticals and pesticides.

The filamentous fungus Penicillium sclerotiorum is significant in ecological and industrial domains due to its vast supply of secondary metabolites that have a diverse array of biological functions. We have gathered the metabolic potential and biological activities associated with P. sclerotiorum metabolites of various structures, based on extensive research of the latest literature. The review incorporated literature spanning from 2000 to 2023, drawing from reputable databases including Google Scholar, ScienceDirect, Scopus, and PubMed, among others. Ranging from azaphilones, meroterpenoids, polyketides, and peptides group exhibits fascinating potential pharmacological activities such as antimicrobial, anti-inflammatory, and antitumor effects, holding promise in pharmaceutical and industrial sectors. Additionally, P. sclerotiorum showcases biotechnological potential through the production of enzymes like β-xylosidases, β-d-glucosidase, and xylanases, pivotal in various industrial processes. This review underscores the need for further exploration into its genetic foundations and cultivation conditions to optimize the yield of valuable compounds and enzymes, highlighting the unexplored potential of P. sclerotiorum in diverse applications across industries.

One new compound, methyl 3-((1-((2-carbamoylphenyl)amino)-1-oxopropan-2-yl)amino)-3-oxopropanoate (1), along with nine known secondary metabolites (2-10) were isolated and elucidated chemical structures from the methanol extract of the marine-derived fungus Penicillium chrysogenum VH17. Subsequent bioassays showed the antimicrobial and cytotoxic potential of the isolated compounds. All compounds 1-10 displayed antimicrobial effects against at least one tested reference microorganism with MIC values ranging from 32 to 256 μg mL-1. Furthermore, compound 4 exhibited significant cytotoxicity against all tested cell lines HepG2, A549, and MCF7 with IC50 values of 29.43 ± 1.37, 33.02 ± 1.53, and 36.72 ± 1.88 µM, respectively, whereas compound 3 exhibited weak cytotoxicity against MCF7 and HepG2 cell lines with IC50 values of 87.17 ± 6.31 and 97.32 ± 5.66 µM, respectively.

Two new polyketide derivatives, penirubenones A and B (1 and 2), and two naturally rare amino-bis-tetrahydrofuran derivatives, penirubenamides A and B (3 and 4), together with nine known compounds (5–13) were isolated from the marine-derived fungus Penicillium rubens BTBU20213035. The structures were identified by HRESIMS and 1D and 2D NMR analyses, and their absolute configurations were determined by a comparison of experimental and calculated electronic circular dichroism (ECD) spectroscopy and 13C NMR data. We found that 6 exhibited antibacterial activity against Staphylococcus aureus, with an MIC value of 3.125 μg/mL, and 1 and 2 showed synergistic antifungal activity against Candida albicans at 12.5 and 50 μg/mL with 0.0625 μg/mL rapamycin.

Bioinformatic analysis revealed that the genomes of ubiquitous Penicillium spp. might carry dozens of biosynthetic gene clusters (BGCs), yet many clusters have remained uncharacterized. In this study, a detailed investigation of co-culture fermentation including the basidiomycete Armillaria mellea CPCC 400891 and the P. brasilianum CGMCC 3.4402 enabled the isolation of five new compounds including two bisabolene-type sesquiterpenes (arpenibisabolanes A and B), two carotane-type sesquiterpenes (arpenicarotanes A and B), and one polyketide (arpenichorismite A) along with seven known compounds. The assignments of their structures were deduced by the extensive analyses of detailed spectroscopic data, electronic circular dichroism spectra, together with delimitation of the biogenesis. Most new compounds were not detected in monocultures under the same fermentation conditions. Arpenibisabolane A represents the first example of a 6/5-fused bicyclic bisabolene. The bioassay of these five new compounds exhibited no cytotoxic activities in vitro against three human cancer cell lines (A549, MCF-7, and HepG2). Moreover, sequence alignments and bioinformatic analysis to other metabolic pathways, two BGCs including Pb-bis and Pb-car, responsible for generating sesquiterpenoids from co-culture were identified, respectively. Furthermore, based on the chemical structures and deduced gene functions of the two clusters, a hypothetic metabolic pathway for biosynthesizing induced sesquiterpenoids was proposed. These results demonstrated that the co-culture approach would facilitate bioprospecting for new metabolites even from the well-studied microbes. Our findings would provide opportunities for further understanding of the biosynthesis of intriguing sesquiterpenoids via metabolic engineering strategies. • Penicillium and Armillaria co-culture facilitates the production of diverse secondary metabolites • Arpenibisabolane A represents the first example of 6/5-fused bicyclic bisabolenes • A hypothetic metabolic pathway for biosynthesizing induced sesquiterpenoids was proposed

Introduction Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties. Methods An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening. Results Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a −10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain. Discussion We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

In connection with their widespread occurrence in diverse environments and ecosystems, fungi in the genus Penicillium are commonly found in association with insects. In addition to some cases possibly implying a mutualistic relationship, this symbiotic interaction has mainly been investigated to verify the entomopathogenic potential in light of its possible exploitation in ecofriendly strategies for pest control. This perspective relies on the assumption that entomopathogenicity is often mediated by fungal products and that Penicillium species are renowned producers of bioactive secondary metabolites. Indeed, a remarkable number of new compounds have been identified and characterized from these fungi in past decades, the properties and possible applications of which in insect pest management are reviewed in this paper.

This study identified secondary metabolites produced by Alternaria alternata, Colletotrichum gloeosporioides and Penicillium digitatum in fruits of two blood orange cultivars before harvest. Analysis was performed by UHPLC–Q-TOF-MS. Three types of fruits were selected, asymptomatic, symptomatic showing necrotic lesions caused by hail, and mummified. Extracts from peel and juice were analyzed separately. Penicillium digitatum was the prevalent species recovered from mummified and hail-injured fruits. Among 47 secondary metabolites identified, 16, 18 and 13 were of A. alternata, C. gloeosporioides and P. digitatum, respectively. Consistently with isolations, indicating the presence of these fungi also in asymptomatic fruits, the metabolic profiles of the peel of hail-injured and asymptomatic fruits did not differ substantially. Major differences were found in the profiles of juice from hail injured and mummified fruits, such as a significant higher presence of 5,4-dihydroxy-3,7,8-trimethoxy-6C-methylflavone and Atrovenetins, particularly in the juice of mummified fruits of Tarocco Lempso cultivar. Moreover, the mycotoxins Patulin and Rubratoxin B were detected exclusively in mummified fruits. Patulin was detected in both the juice and peel, with a higher relative abundance in the juice, while Rubratoxin B was detected only in the juice. These findings provide basic information for evaluating and preventing the risk of contamination by mycotoxins in the citrus fresh fruit supply chain and juice industry.

Filamentous fungi are an important source of natural products. The mold Penicillium roqueforti, which is well-known for being responsible for the characteristic texture, blue-green spots, and aroma of the so-called blue-veined cheeses (French Bleu, Roquefort, Gorgonzola, Stilton, Cabrales, and Valdeón, among others), is able to synthesize different secondary metabolites, including andrastins and mycophenolic acid, as well as several mycotoxins, such as Roquefortines C and D, PR-toxin and eremofortins, Isofumigaclavines A and B, festuclavine, and Annullatins D and F. This review provides a detailed description of the biosynthetic gene clusters and pathways of the main secondary metabolites produced by P. roqueforti, as well as an overview of the regulatory mechanisms controlling secondary metabolism in this filamentous fungus.

The continuous burden of human immunodeficiency virus-1 in Sub-Saharan Africa, coupled with the inability of antiretroviral agents to eradicate HIV-1 from viral reservoirs, the potential risks of drug resistance development, and the development of adverse effects, emphasizes the need to develop a new class of HIV-1 inhibitors. Here, we cultivated four endophytic fungal isolates from a medicinal plant, Albizia adianthifolia with the addition of small epigenetic modifiers, sodium butyrate, and valproic acid, to induce the expression of biosynthetic gene clusters encoding active secondary metabolites with probable anti-HIV activities. We identified a non-toxic crude extract of the endophytic fungus Penicillium chrysogenum treated with sodium butyrate to possess significantly greater anti-HIV activity than the untreated extracts. Penicillium chrysogenum P03MB2 showed anti-HIV activity with an IC50 of 0.6024 µg/mL compared to untreated fungal crude extract (IC50 5.053 µg/mL) when treated with sodium butyrate. The profile of secondary metabolite compounds from the bioactive, partially purified extracts were identified by gas chromatography-mass spectrometry (GC-MS), and more bioactive compounds were detected in treated P. chrysogenum P03MB2 fractions than in untreated fractions. Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro (13.64%), cyclotrisiloxane, hexamethyl (8.18%), cyclotetrasiloxane, octamethyl (7.23%), cyclopentasiloxane, decamethyl (6.36%), quinoline, 1,2-dihydro-2,24-trimethyl (5.45%), propanenitrile (4.55%), deca-6,9-diene (4.55%), dibutyl phthalate (4.55%), and silane[1,1-dimethyl-2-propenyl)oxy]dimethyl (2.73%) were the most abundant compounds. These results indicate that treatment of endophytic fungi with small epigenetic modifiers enhances the secretion of secondary metabolites with stronger anti-HIV-1 properties, acknowledging the feasibility of epigenetic modification as an innovative approach for the discovery of cryptic fungal metabolites which can be developed into therapeutic compounds.

Endophytic fungi produced attractive primary and secondary metabolites for industries, pharmacology, and biotechnology. The bioactive potential of HE19ct, identified as Penicillium brevicompactum according to ITS-BenA-caM, was addressed. Antimicrobial and antioxidant activities and secondary metabolite contents using four culture media in Agar-plate (ApF) and Submerged (SmF) fermentation were evaluated. Some plant growth-promoting (PGP) traits and their related genes were tested. HE19ct exhibited antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Candida albicans, C. tropicalis, Fusarium sp., Geotrichum candidum, and Alternaria sp. All cultures showed DPPH scavenging activity and phenolic compounds, where ethyl acetate extract of SmF with malt extract showed higher activity and SmF/ApF with potato-dextrose exhibited higher yield, respectively. HE19ct solubilized tricalcium-phosphate and produced siderophore, endoglucanase, proteinase, and amylase. It enhanced the alfalfa's germination at 15 °C, root development, and phenols production at 15 and 24 °C. Phenols, tannins, anthraquinones, triterpenoids/steroids, and alkaloids production were detected depending on culture media. Polyketide synthase type I gene (PksI), subtilisin-like protease prb 1 (Pbr), and siderophore D (sidD) were PCR-amplified. Finally, HE19CT could be a promising source of interesting bioactive compounds for pharmacology and agriculture mainly in extreme conditions, then metabolomic and functional genetic research must be performed to support their appropriate application.

Penicillium roqueforti is a fungal starter culture used for the production of blue-veined cheeses, such as Roquefort, Gorgonzola, Stilton, Cabrales, and Danablue. During ripening, this species grows in the veins of the cheese, forming the emblematic blue-green color and establishing the characteristic flavor owin to its biochemical activities. P. roqueforti synthesizes a diverse array of secondary metabolites, including the well-known compounds roquefortine C, clavine alkaloids, such as isofumigaclavine A and B, mycophenolic acid, andrastin A, and PR-toxin. This review provides an in-depth exploration of P. roqueforti’s secondary metabolites, focusing on their biosynthetic pathways, the gene clusters responsible for their production, and their bioactivities. The presence of these compounds in blue cheeses is also reviewed. Furthermore, the silent clusters and the potential of P. roqueforti for producing secondary metabolites were discussed. The review highlights recently identified metabolites, including sesterterpenoids; tetrapeptides, D-Phe-L-Val-D-Val-L-Tyr, and D-Phe-L-Val-D-Val-L-Phe; cis-bis(methylthio)silvatin; and the 1,8-dihydroxynaphthalene (DHN)-melanin precursor, scytalone. Additionally, a gene cluster for DHN–melanin biosynthesis is presented. Finally, a revised cluster for roquefortine C biosynthesis comprising three rather than four genes is proposed.

No abstract available

Bioreactor cocultures involving Penicillium rubens and Streptomyces rimosus were investigated with regard to secondary metabolite production, morphological development, dissolved oxygen levels, and carbon substrate utilization. The production profiles of 22 secondary metabolites were analyzed, including penicillin G and oxytetracycline. Three inoculation approaches were tested, i.e., the simultaneous inoculation of P. rubens with S. rimosus and the inoculation of S. rimosus delayed by 24 or 48 h relative to P. rubens. The delayed inoculation of S. rimosus into the P. rubens culture did not prevent the actinomycete from proliferating and displaying its biosynthetic repertoire. Although a period of prolonged adaptation was needed, S. rimosus exhibited growth and the production of secondary metabolites regardless of the chosen delay period (24 or 48 h). This promising method of coculture initiation resulted in increased levels of metabolites tentatively identified as rimocidin B, 2-methylthio-cis-zeatin, chrysogine, benzylpenicilloic acid, and preaustinoid D relative to the values recorded for the monocultures. This study demonstrates the usefulness of the delayed inoculation approach in uncovering the metabolic landscape of filamentous microorganisms and altering the levels of secondary metabolites.

This study aims to identify and assess the antimicrobial activity of endophytic fungi found in the endemic plant Abies numidica . Among all isolates, the ANT13 isolate demonstrated significant antimicrobial activity in the preliminary screening, particularly Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 1024, with inhibition zones of 22 and 21.5 mm, respectively. Based on its morphological and molecular features, this isolate was identified as Penicillium brevicompactum . The maximum activity was observed in the ethyl acetate extract, followed by the dichloromethane extract; however, the n-hexane extract exhibited no activity. The ethyl acetate extract demonstrated very significant activity against the five strains of multidrug-resistant Staphylococcus aureus used, with average zones of inhibition ranging from 21 to 26 mm, in contrast to more resistant Enterococcus faecalis ATCC 49452 and Bacillus cereus ATCC 10876. The ethyl acetate extract was also very active against dermatophytes, where the zones of inhibition for Candida albicans , Microsporum canis , Trichophyton mentagrophytes , Trichophyton rubrum, and Epidermophyton floccosum were 23.5, 31, 43, 47, and 53.5 mm, respectively. The MIC values for dermatophytes ranged between 100 and 3200 µg/mL. The wild isolate of Penicillium brevicompactum ANT13 discovered as an endophyte in Abies numidica may be a distinctive source of novel compounds and drug discovery to trait dermatophytes and multidrug-resistant Staphylococcus aureus infections.

No abstract available

Endophytes are an attractive source of natural products with distinctive structures that can aid in the treatment of life-altering disorders because of the complexity and structural variety of the secondary metabolites that they produce. The genus Penicillium , which belongs to family Aspergillaceae, class Eurotiomycetes has received more attention due to the isolation of various classes of compounds with unique structures mainly such as alkaloids, amides, ceramides, naphthoquinone derivatives, sterols, tetracyclic triterpenes, penostatins, phenalenones, phenolic compounds, diphenyl ethers, glycerol derivatives, cytochalasan derivatives, pyrone and pyrrolidine derivatives. They exhibited diverse biological activities as: anticancer, antimicrobial, cardiovascular, anti-inflammatory and neuroprotective. This review focuses on the isolated secondary metabolites from genus Penicillium, the source of the strains and the biological potential of isolated secondary metabolites. It covers the literature from 2010 to 2024.

Diethyl sulfate (DES)-based chemical mutagenesis was applied on different fungal strains with the aim of diversifying the secondary metabolites. The mutant strain (VRE-MT1) of Penicillium oxalicum was subjected to dereplication (LCMS-based) and isolation of natural products, resulting in obtaining 10 molecules of bioactive potential. Metabolites, viz. tuckolide, methylpenicinoline, 2-acetyl-3,5-dihydroxy-4,6-dimethylbenzeneacetic acid, penicillixanthone A, brefeldin A 7-ketone, and antibiotic FD 549, were observed for the first time from P. oxalicum. The results of antimicrobial activity reveal that the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A have potent antibacterial activity against Bacillus subtilis (ATCC 6633) with minimum inhibitory concentration (MIC) values of 16, 64, and 16 μM, respectively, and the compounds N-[2-(4-hydroxyphenyl)ethenyl]formamide, methylpenicinoline, and penipanoid A were found active against Escherichia coli (ATCC 25922), with MIC values of 16, 64, and 16 μM, respectively. Also, the metabolites N-[2-(4-hydroxyphenyl)ethenyl]formamide and tuckolide showed effective antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid scavenging assays. The mutant VRE-MT1 was found to have 8.34 times higher quantity of N-[2-(4-hydroxyphenyl)ethenyl]formamide as compared to the mother strain. The DES-based mutagenesis strategy has been found to be a potent tool to diversify the secondary metabolites in fungi.

Marine-derived Penicillium fungi are one of the most important sources for the discovery of new bioactive natural products. This study characterized the isolation, structures, and antiglioma activities of twelve compounds, including three novel ones—penipyridinone B (1), 11S-(−)-penilloid A (2), and 11R,14E-(+)-penilloid A (3)—from the marine fungus Penicillium sp. ZZ1750. The structures of the novel compounds were determined via extensive nuclear magnetic resonance (NMR) spectroscopic analyses, high-resolution electrospray ionization mass spectroscopy (HRESIMS) data, Mosher’s method, optical rotation (OR) calculations, and electronic circular dichroism (ECD) calculations. Penipyridinone B represents the first example of its structural type and showed potent antiglioma activity, with IC50 values of 2.45 μM for U87MG cells and 11.40 μM for U251 cells. The known compounds of questiomycin A (9) and xanthocillin X (10) also showed antiproliferative activity against both U87MG and U251 cells, with IC50 values of 13.65 μM to 22.56 μM. The antiglioma activity of questiomycin A and xanthocillin X may be related to the promotion of reactive oxygen species (ROS) production, the reduction of mitochondrial membrane potential (MMP), and the enhancement of caspase-3 enzyme activity.

No abstract available

The endophytic fungus Penicillium is an important source of natural bioactive products. Persicaria salicifolia (Brouss. ex Willd) (family Polygonaceae) is a widely distributed plant on the Nile River and was reported to have several biological activities, such as antioxidative, antibacterial, and anti-inflammatory effects. This study aimed to explore the potential activities (cytotoxic, anti-oxidant, and anti-microbial) of the endophytic fungus Penicillium funiculosum isolated from Persicaria salicifolia seeds growing in Egypt. The endophytic fungus Penicillium funiculosum was isolated from the seeds of the Persicaria salicifolia plant. The fungi were grown on Basmati rice as a solid media for the enhancement of pure fungi production. The collected fungi were extracted with ethyl acetate and fractionated using n-hexane and methanol. All fractions were examined for their cytotoxic, antioxidant, and antimicrobial activities. The secondary metabolites were isolated from the active fractions through column chromatography, and the isolated compounds were identified by spectroscopic technique. Molecular docking analysis was applied to the isolated compounds. Ethyl acetate extract (Pf-2) of P. funiculosum was proved to have a highly potent antioxidant (IC50 37.5±0.70 μg/ml) and cytotoxic effects. It was affected on hepatic cancer (HepG-2), human colon carcinoma (HCT-116), lung carcinoma (A-549), and human breast cancer (MCF-7) cells with IC50 values (μg/ml) 4.26±0.2, 6.66±0.9, 9.36±0.3, and 9.41±0.7, respectively. Pf 2 was subjected to fractionation, resulting in four fractions (Pf 2–1 to Pf 2–4). The most potent cytotoxic fraction, Pf 2–2, was further fractionated into six sub-fractions: Pf 2–2 A to Pf 2–2 F. Pf 2–2 A possessed the most potent cytotoxic activity. The ethyl acetate extract (Pf 2) also had antimicrobial activity against gram-positive Bacillus subtilis and gram-negative bacteria (E. coli). Four compounds were isolated from Pf 2–2 A and identified by spectroscopic methods: NMR (1H and 13C) and Mass as (1) (9E, 11E, 13Z, 15Z)-tetracosa-9, 11, 13, 15-tetraenoic acid, (2) 3-(1Z, 3E-hexa-1, 3-dienyl)-4b-methyl-tetradecahydrophenanthrene, (3) mannitol, (4) d-Cerebroside A-glucose. It is the first time to report the isolation of compound (2) from the genus Penicillium and compounds (1, 3, and 4) from the species P. funiculosum. Compound 2 was the most potent cytotoxic one. Molecular docking was studied for polar compounds 1, 3, and 4 using the COX-2 enzyme, which indicated that compound 4 was the most potent anti-inflammatory one.

Two new natural products have been isolated from culture broth of Penicillium brevicompactum Dierckx. The structures have been assigned as N-(2-methyl-3-oxodecanoyl)pyrrole and N-(2-methyl-3-oxodec-8-enoyl)pyrrole on the basis of spectral data. Synthesis of analogues has been carried out by acylation of the pyrrole ring at C2 with different acylated Meldrum's acids. Two analogues (6b and 7b) have shown interesting insecticidal activities, and three other ones (6a, 6c, and 7a) have exhibited significant broad-spectrum fungicidal activities. These synthetic products might be considered as a starting point in the search for new pesticides. Keywords: Penicillium brevicompactum; fungal metabolites; Meldrum's acid; 2-(3-oxoacyl)pyrrole; insecticide; fungicide

MS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products. In the present study, the chemical diversity of indole diterpenoids from the marine-derived fungus Penicillium sp. N4-3 was investigated using molecular networking techniques. Guided by this information, targeted isolation resulted in two new indole diterpenoids shearinines R and S (1, 2) and an oxidative artifact shearinine T (3), together with the verification of two known analogs (4, 5). Furthermore, five indole diterpenoids (6−10), including three putatively new ones, shearinines U−W (6, 9, 10), were predicted from the molecular ion cluster by the combination of GNPS molecular networking and manual analysis of MS/MS fragmentation clusters. Shearinines T (3) and W (10) are characterized by an oxidative cleavage of the C-2–C-18 double bond. Feature fragment ions of these shearinines revealed two type of dominant ions related to the indole moiety and the breaking of C-9 side chain or Ring I. Compound 1 showed antibacterial activities against a panel of pathogenic bacteria with IC50 values ranging from 6.34 to 47.96 μg/mL and inhibited the growth of the human hepatic (HepG2) and gastric (SGC-7901) cancer cells lines with IC50 values of 6.27 and 19.16 μg/mL, respectively.

OSMAC (one strain many compounds) provides a convenient strategy to produce chemically diverse and novel natural products. In the study, the application of an OSMAC approach on a fungus Penicillium citrinum YSC-1 isolated from a medicinal plant Chloranthus japonicus, using different culture media, led to the isolation and identification of seven new spirooxindole alkaloids penicitrimicins A-G (1-7) with a rare 6/5/5/6/6 polycyclic skeleton, along with two known compounds (8-9). The new structures were characterized based on the comprehensive spectroscopic analyses, including 1D, 2D NMR and HRESIMS data. The absolute configurations of compounds 1-7 were determined by modified Mosher ester methodology, PGME derivatization, X-ray crystallographic analysis, and quantum chemical calculations. Biological evaluation revealed that these spirooxindole alkaloids exhibited good biocompatibility (<5 % hemolysis and > 80 % cell viability) while displaying obvious antimalarial activity against Plasmodium falciparum Dd2 strain, with EC50 values spanning 0.9-2.4 μM. Furthermore, stage-specific assays revealed that compound 5 displayed significant inhibitory effects on the developmental transition of asexual blood-stage parasites, effectively blocking their progression to subsequent lifecycle stages.

SARS-CoV-2 virus mutations might increase its virulence, and thus the severity and duration of the ongoing pandemic. Global drug discovery campaigns have successfully developed several vaccines to reduce the number of infections by the virus. However, finding a small molecule pharmaceutical that is effective in inhibiting SARS-CoV-2 remains a challenge. Natural products are the origin of many currently used pharmaceuticals and, for this reason, a library of in-house fungal extracts were screened to assess their potential to inhibit the main viral protease Mpro in vitro. The extract of Penicillium citrinum, TDPEF34, showed potential inhibition and was further analysed to identify potential Mpro inhibitors. Following bio-guided isolation, a series of benzodiazepine alkaloids cyclopenins with good-to-moderate activity against SARS-CoV-2 Mpro were identified. The mode of enzyme inhibition of these compounds was predicted by docking and molecular dynamic simulation. Compounds 1 (isolated as two conformers of S- and R-isomers), 2, and 4 were found to have promising in vitro inhibitory activity towards Mpro, with an IC50 values range of 0.36–0.89 µM comparable to the positive control GC376. The in silico investigation revealed compounds to achieve stable binding with the enzyme active site through multiple H-bonding and hydrophobic interactions. Additionally, the isolated compounds showed very good drug-likeness and ADMET properties. Our findings could be utilized in further in vitro and in vivo investigations to produce anti-SARS-CoV-2 drug candidates. These findings also provide critical structural information that could be used in the future for designing potent Mpro inhibitors.

In our study, chemical investigation of the marine fungus Penicillium sp. led to the isolation of four isocoumarin derivatives, including two new compounds (1 and 2) and two known analogues (3 and 4). The structures of 1 and 2 were determined by comprehensive analysis of the 1D (1H and 13C NMR spectra) and 2D NMR data (COSY, HSQC, HMBC, and NOESY spectra). The structure of 1 was confirmed by comparing the calculated and experimental 13C NMR data. Compounds 1 and 2 are isocoumarins that lack substitution at the C‐5, C‐6, and C‐7 positions, a structural feature that is uncommon among this class of natural products. The current study enriched the chemical diversity of fungus‐derived isocoumarin derivatives.

Chemical investigation of the fungus Penicillium sp. KYS-21 resulted in the isolation of 16 new curvulinic acid-gregatin hybrids (CAGHs), penicurgretides A-P (1-16), together with the only known analogue (17) of this rare class of natural products. Their structures were unambiguously determined by comprehensive spectroscopic analyses, ECD calculations, single-crystal X-ray diffraction, and the modified Mosher's method. These hybrids exhibit remarkable diversity, featuring a conserved R-configuration at C-5 but variable stereochemistry at other chiral centers. The α,β,γ,δ-unsaturated ketone in the C-5 side chain was established as a critical pharmacophore, as penicurgretides A (1) and G (7), bearing this moiety, exhibited moderate anti-inflammatory activity with IC50 values of 2.94 ± 0.54 and 3.50 ± 0.52 μM, respectively. Mechanistic studies revealed that penicurgretide A (1) suppresses inflammation through inhibition of the NF-κB and mitogen-activated protein kinase signaling pathways, with in vivo efficacy confirmed by reducing nitric oxide and ROS production in an LPS-induced zebrafish model. These findings expand the structural diversity of CAGHs and highlight penicurgretide A (1) as a promising lead for anti-inflammatory drug development.

Traditional isolation methods often lead to the rediscovery of known natural products. In contrast, genome mining strategies are considered effective for the continual discovery of new natural products. In this study, we discovered a unique prenyltransferase (PT) through genome mining, capable of catalyzing the transfer of a prenyl group to an aromatic nucleus to form C-C or C-O bonds. A pair of new hydroxyphenylacetic acid derivative enantiomers with prenyl units, (±)-peniprenydiol A (1), along with 16 known compounds (2–17), were isolated from a marine fungus, Penicillium sp. W21C371. The separation of 1 using chiral HPLC led to the isolation of the enantiomers 1a and 1b. Their structures were established on the basis of extensive spectroscopic analysis, including 1D, 2D NMR and HRESIMS. The absolute configurations of the new compounds were determined by a modified Mosher method. A plausible biosynthetic pathway for 1 was deduced, facilitated by PT catalysis. In the in vitro assay, 2 and 3 showed promising inhibitory activity against Escherichia coli β-glucuronidase (EcGUS), with IC50 values of 44.60 ± 0.84 μM and 21.60 ± 0.76 μM, respectively, compared to the positive control, D-saccharic acid 1,4-lactone hydrate (DSL). This study demonstrates the advantages of genome mining in the rational acquisition of new natural products.

A detailed chemical study of the culture of a coral-derived fungus Penicillium chrysogenum resulted in the isolation and identification of four new aromatic heterocycles chrysoquinazolinones A–B (1–2) and chrysobenzothiazoles A–B (3–4), along with a new sorbicillinoid 4-carboxylsorbicillin (5). Chrysoquinazolinones A–B (1–2) combine a quinazolinone fragment with a bicyclo[2.2.2]octane or a pyrrolidone moiety, respectively, demonstrating the unexpected structures of marine natural products. Chrysobenzothiazoles A–B (3–4) possess a benzothiazole system and are the second isolation of this class of skeleton compounds from marine organisms. The existence of the pair of enantiomers (±3) was deduced by chiral HPLC analysis. Their structures and absolute configurations were elucidated by detailed spectroscopic analysis, comparison with the literature data, single-crystal X-ray crystallographic analysis and TDDFT-ECD calculations. Compound 5 exhibited moderate cytotoxicity against K562 and NCI-H446 cell lines, with IC50 values of 15.00 μM and 16.87 μM, respectively.

Penicillium daleae L3SO is a fungus isolated from the rhizospheric soil of the chloroplast-deficient plant Monotropa uniflora. A chemical study on the rice fermentation of this fungus led to the isolation and identification of two cage-like polyketides, penidaleodiolide A (1) and its biosynthetic-related congener penidaleodiolide B (2). The structures of 1 and 2 were determined by a combination of extensive spectroscopic analysis, biosynthetic consideration, chemical derivatization, and computational methods. Compound 1 harbors an unusual tricyclo[4.3.04,9]nonane scaffold, unprecedented in polyketide natural products. The hypothetical biosynthetic pathways for 1 and 2 were postulated and were supported by CRISPR/Cas9 genome editing results. Penidaleodiolide A (1) showed a significant inhibitory effect on the action potentials of murine hippocampal basket neurons and decreased the frequency of spontaneous excitatory postsynaptic currents in a concentration-dependent manner (the inhibition ratios were 0.30 ± 0.02 for 1 μM, 0.37 ± 0.03 for 10 μM, and 0.50 ± 0.07 for 20 μM) while being devoid of cytotoxicity against the nerve cells.

Marine fungal natural products are valuable sources of structurally diverse and biologically active compounds with potential applications in drug discovery and biotechnology. The fungus Penicillium crustosum is an important source of bioactive natural products that display significant antibacterial properties. This study describes the isolation and characterization of two new structures including one γ‐unsaturated lactone named crustosulin A and one aliphatic acid named crustosenoic acid A along with ten known compounds from a marine‐derived fungus Penicillium crustosum HDN17‐68, which is isolated from the Western Pacific deep‐sea mud sample. Compounds were isolated and purified through column chromatography and HPLC, and structures were elucidated using spectroscopic tools including NMR, MS, and ECD. Compound 1 represents the first example of a dimeric γ‐unsaturated butyrolactone incorporating a β‐to‐α connectivity and it exhibited weak activity against Salmonella enterica and methicillin‐resistant Staphylococcus aureus (MRSA), with MIC values of 32 and 64 µg/mL, respectively. These findings expand the chemical diversity of secondary metabolites from deep‐sea‐derived Penicillium fungi.

Chemical examination of a marine sponge-associated Penicillium copticola fungus resulted in the isolation of ten undescribed eremophilanes, namely copteremophilanes A–J (1–10), along with two new glycosides, 5-glycopenostatin F (11) and 5-glucopenostatin I (12). Their structures were determined by extensive spectroscopic data, in association with ECD data and chemical conversions for configurational assignments. Analogs 1, 2, and 10 represent a group of uncommon skeletons of eremophilanes with an aromatic ring and a methyl migration from C-5 to C-9, and analogs 11 and 12 are characteristic of a PKS scaffold bearing a glucose unit. The incorporation of a chlorinated phenylacetic unit in 3–9 is rarely found in nature. Analog 7 showed neuroprotective effect, whereas 8 exhibited selective inhibition against human non-small cell lung cancer cells (A549). This study enriched the chemical diversity of eremophilanes and extended their bioactivities to neuroprotection.

Tyrosinase is a copper-containing monooxygenase catalyzing the O-hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine then to dopaquinone that is profoundly involved in melanin synthesis in eukaryotes. Overactivation of tyrosinase is correlated with hyperpigmentation that is metabolically correlated with severe pathological disorders, so, inhibition of this enzyme is the most effective approach in controlling the overproduction of melanin and its hazardous effects. Thus, searching for a powerful, selective inhibitor of human tyrosinase to limit the hyper-synthesis of melanin is a challenge. Unlike the difficulty of overexpression of human tyrosinase, using fungal tyrosinase as a model enzyme to the human one to evaluate the mechanistics of enzyme inhibition in response to various compounds is the most feasible strategy. Thus, the purification of highly catalytic-efficient fungal tyrosinase, exploring a novel inhibitor, and evaluating the mechanistics of enzyme inhibition are the main objectives of this work. Aspergillus terreus and Penicillium copticola were reported as the most potential tyrosinase producers. The biochemical properties suggest that this enzyme displays a higher structural and catalytic proximity to human tyrosinase. Upon nutritional bioprocessing by Plackett–Burman design, the yield of tyrosinase was increased by about 7.5-folds, compared to the control. The purified tyrosinase was strongly inhibited by kojic acid and A. flavus DCM extracts with IC50 values of 15.1 and 12.6 µg/mL, respectively. From the spectroscopic analysis, the main anti-tyrosinase compounds of A. flavus extract was resolved, and verified as undecanoic acid. Further studies are ongoing to unravel the in vivo effect and cytotoxicity of this compound in fungi and human, that could be a novel drug to various diseases associated with hyperpigmentation by melanin.

No abstract available

The chemical composition, security and bioactivity of pigments from Penicillium purpurogenum Li‐3 strain screened by our group were firstly studied in this work. DPPH and the filter disc diffusion method were used to determine the biological activities of the red pigments. The pigment was characterized by UV/VIS, FT‐IR, NMR and UPLC‐Q‐TOF‐MS. HPLC/MS was used to detect mycotoxins (citrinin) in fermentation broth. An acute toxicity was detected in the embryos of zebrafish. As a consequence, the crude red pigment from the AcOEt fraction showed better DPPH scavenge capacity and antibacterial activity. Spectroscopic (UV, FT‐IR, 13C‐NMR) and UPLC‐Q‐TOF‐MS analysis revealed that the Penicillium purpurogenum Li‐3 red pigment (RPs) was monascus‐like pigment and its molecular weight was 439.1997. Moreover, the red pigment was shown to be weak cytotoxic against the zebrafish embryos. The yield of the red pigment increased 69 % under optimized culture conditions. These outstanding properties will enlarge the application of RPs for natural food additives, new antioxidant and antibacterial drug development.

Marine fungi, such as species from the Penicillium and Aspergillus genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC50 values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.

Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B ( 1 ) and C ( 2 ) together with known saroclazin A ( 3 ) (4 S ,5 R ,7 S )-4,11-dihydroxy-guaia-1(2),9(10)-dien ( 4 ). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B ( 1 ) as 2 R ,5 R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed. Graphical Abstract

To isolate and characterize antitumor active compounds (bioactivity-guided fractionation) from the ethyl acetate extract of fermentation broth of marine-derived fungus Penicillium chrysogenum HGQ6. Following the cytotoxicity against human cancer cell line BGC823, one compound was isolated and purified by silica gel chromatography, Sephadex LH-20 chromatography and preparative high performance liquid chromatography. The isolated compound was elucidated on the basis of extensive spectroscopic data analysis as 5-hydroxymethyl-2furancarboxaldehyde, which exhibited cytotoxicity against BGC823 cell line with an IC50 value of 0.19 mg/mL. Our present study concluded that, 5-Hydroxymethyl-2-furancarboxaldehyde isolated from marine-derived fungus Penicillium chrysogenum HGQ6 has a certain extent of antitumor potential.

One new monomeric citrinin analog (1) and 42 known compounds (2–43) were isolated from Penicillium citrinum W22. The structure of 1 was determined by detailed analysis of the 1D and 2D nuclear magnetic resonance (NMR), HRESIMS, and time‐dependent density functional theory (TD‐DFT)‐based electronic circular dichroism (ECD) calculation. Penicitrinol A (2) and methyl 2‐(2‐acetyl‐3,5‐dihydroxy‐4,6‐dimethylphenyl) acetate (11) significantly inhibited renin‐angiotensin system‐selective lethal 3 (RSL3)‐induced ferroptosis with half maximal effective concentration (EC50) values of 1.6 and 34.0 µM, respectively.

A rare tri‐nor‐non‐paspaline indole diterpenoid (penpaxin A, 1), a new 1,3‐dioxolane derivative (penpaxin B, 9), and 19 known compounds (2–8 and 10–21) were isolated from the deep‐sea‐derived Penicillium paxilli MCCC 3A01133. The structures of the new compounds were established by detailed analyses of the NMR, HRESIMS, and ORD data. 3‐Deoxo‐4b‐deoxypaxilline (5) and paspaline (7) exhibited potent inhibition on RSL3‐induced ferroptosis with the EC50 values of 2.88 and 0.21 µM, respectively.

From the agar-based culture of the marine-derived Penicillium sp. M839 strain, nine known compounds were isolated and structurally determined, including fumiquinazoline D (1), fumiquinazoline B (2), cerevisterol (3), stoloniferol B (4), norhaman (5), 3,4-dihydroxy-6,7-dimethyl-quinolin-2-carboxylic (6), uracil (7), 3-methyl uracil (8), thymine (9). These compounds were characterized via 1D and 2D NMR spectroscopic and mass spectrometric analyses. Compounds 2 and 8 were first recognized from the genus Penicillium, while the remaining compounds were previously isolated from this genus. Compounds 1–6 were evaluated for their antimicrobial activity against a panel of test microorganisms (three Gram-positive bacteria: Enterococcus faecalis, Staphylococcus aureus, Bacillus cereus; three Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica and one yeast strain Candida albicans). The results showed that compound 6 displayed strong antimicrobial activity against two Gram-negative bacteria E. coli and S. enterica, with the MIC values of 32 and 64 µg/mL, respectively. In addition, the remaining compounds 1–5 inhibited against all test microorganisms with MIC values ranging from 64 to 256 µg/mL.

Abstract Phytochemical investigation on the plant endophytic fungus Penicillium ferraniaense GE-7 led to the isolation of 18 compounds including one new α-pyrone derivative, peniferranige A (1). The structure including the absolute configuration of compound 1 was elucidated by NMR, HRMS, and ECD data. Demethoxyfumitremorgin C (16) and meleagrin (17) possessed moderate activities against the human lung cancer cell line H1975 with IC50 values of 28.52 ± 1.07 and 13.94 ± 1.92 μM, respectively. Graphical Abstract

One new alkaloid, (S)‐2‐acetamido‐4‐(2‐(methylamino)phenyl)‐4‐oxobutanoic acid (1), was isolated from the deep‐sea‐derived Penicillium citrinum XIA‐16, together with 25 known compounds including ten polyketones (2–11), eight alkaloids (12–19), six steroids (20–25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR‐ESI‐MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3‐induced ferroptosis (EC50=2.0 μM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 μM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.

Chemical examination of Penicillium steckii HJT-A-10, an endophytic fungus derived from Rhodiola tibetica, led to the isolation of ten metabolites. Structural elucidation by spectroscopic methods revealed that two of these were previously unreported compounds (1 and 2), though the absolute stereochemistry of 2 remained provisional; the other eight isolates (3–10) were identified as known compounds. All ten metabolites were tested for their capacity to inhibit nitric oxide (NO) production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Compounds 1–4 and 7–10 exhibited marked inhibitory effects. Among the two new compounds, 2 displayed stronger activity, with an IC50 value of 19.01 µM. To explore the potential mechanisms of action, network pharmacology and molecular docking analyses were subsequently conducted to predict the relevant targets and signaling pathways.

Three previously undescribed compounds (1–3), including an unusual pyridazine derivative, one sesquiterpenoid, and a polyketide with novel stereochemistry, together with 24 known compounds (4–27), were isolated from the deep‐sea‐derived Penicillium limosum ZEN48. The structures of the new compounds were elucidated by comprehensive analyses of one‐ and two‐dimensional nuclear magnetic resonance, high‐resolution electrospray ionization mass spectrometry, and optical rotation calculation. Compounds 13, 18, and 19 exhibited considerable inhibitory effect in osteoclast formation at 20 µM in bone marrow‐derived monocytes, indicating their potential application in anti‐osteoporotic therapy.

Marine natural products are well‐recognized as potential resources to fill the pipeline of drug leads to enter the pharmaceutical industry. In the present study, one new γ‐butyrolactone derivative (1), together with 20 known compounds (2–21), were isolated from an Penicillium roseopurpureum, isolated from sediments collected from the Atlantic. Compounds 2 and 3 were registered in SciFinder under CAS registry numbers 1823883‐92‐6 and 2386376‐03‐8, respectively. However, no characterization data, spectral information, or references are available for either compound. Their structures were determined by detailed analysis of the 1D and 2D NMR, HRESIMS, and NMR calculations with DP4+ probability analysis, as well as ORD calculations. The anti‐neuroinflammatory effects of all isolates were assessed in lipopolysaccharide (LPS)‐stimulated BV‐2 microglial model. Remarkably, compound 13 exhibited notable anti‐neuroinflammatory activity with IC50 values of 6.72 µM.

Two new polyketides (1–2) were isolated from the deep‐sea‐derived fungus Penicillium citrinum W17, along with 39 known compounds (3‐41). The structures were established by 1D and 2D NMR, HRESIMS data analysis. Compounds 10, 35, and 36 displayed potent inhibitory effects against RSL3‐induced ferroptosis with EC50 values of 2.7 µM, 4.9 µM, and 5.4 µM, respectively.

One new citrinin derivative (1) and one new fatty acid (27) were isolated from the marine Penicillium citrinum W24, together with 29 known compounds. Their structures were determined by extensive spectroscopic analysis. Compound 7 showed potent ferroptosis inhibitory activity with an EC50 value of 0.22 μM.

Six new citreoviridins (citreoviridins J–O, 1–6) and twenty-two known compounds (7–28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J−O (1–6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2–C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC50 values of 5.4 μM, 11.3 μM, and 0.7 μM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.

In this study, a marine brown alga Sargassum cristaefolium-derived fungal strain, Penicillium sumatraense SC29, was isolated and identified. Column chromatography of the extracts from liquid fermented products of the fungal strain was carried out and led to the isolation of six compounds. Their structures were elucidated by spectroscopic analysis and supported by single-crystal X-ray diffraction as four previously undescribed (R)-3-hydroxybutyric acid and glycolic acid derivatives, namely penisterines A (1) and C–E (3–5) and penisterine A methyl ether (2), isolated for the first time from natural resources, along with (R)-3-hydroxybutyric acid (6). Of these compounds identified, penisterine E (5) was a unique 6/6/6-tricyclic ether with an acetal and two hemiketal functionalities. All the isolates were subjected to in vitro anti-angiogenic assays using a human endothelial progenitor cell (EPCs) platform. Among these, penisterine D (4) inhibited EPC growth, migration, and tube formation without any cytotoxic effect. Further, in in vivo bioassays, the percentages of angiogenesis of compound 3 on Tg (fli1:EGFP) transgenic zebrafish were 54% and 37% as the treated concentration increased from 10.2 to 20.4 µg/mL, respectively, and the percentages of angiogenesis of compound 4 were 52% and 41% as the treated concentration increased from 8.6 to 17.2 µg/mL, respectively. The anti-angiogenic activity of penisterine D (4) makes it an attractive candidate for further preclinical investigation.

A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide (1), two new alkaloids (2 and 3), and 22 known (4–25) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol (13) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC50 values of around 20 μM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC50 value of 13 μM, compared to that of 92 μM for the positive control, loratadine, while indole-3-acetic acid methyl ester (9) and penicopeptide A (10) showed moderate effects (IC50 = 50 and 58 μM, respectively).

One new (d‐arabinitol‐anofinicate, 1) and fourteen known (2–15) compounds were isolated from the marine Penicillium sp. MCCC 3A00228. The structure of the new compound was established mainly by extensive spectroscopic analyses. Compound 1 exhibited weak transcriptional effect on Nur77. While compound 13 showed moderate in vitro anti‐proliferative effect against QGY7701, H1299, and HCT116 tumor cells with IC50 values of 21.2 μM, 18.2 μM, and 17.6 μM, respectively.

No abstract available

A new azo compound, penoxalin (1), a new isochroman carboxylic acid, penisochroman B (3), two new natural products, penisochroman A (2) and 2,6-dihydroxy-4-[(2R)-2-hydroxyheptyl] benzoic acid (4), together with four known compounds (5-8) were isolated from wetland soil fungus Penicillium oxalicum GY1. All structures were elucidated by extensive NMR spectroscopic evidences together with mass spectrometry. The absolute configuration of penoxalin (1) was determined by calculated ECD spectrum, while the absolute configuration of new natural product penisochroman A (2) was established for the first time by single crystal X-ray diffraction. In addition, all compounds were evaluated for their cytotoxic activity in vitro. 2, 6-Dihydroxy-4-[(2R)-2-hydroxyheptyl] benzoic acid (4) displayed significant cytotoxicity against human esophageal carcinoma cells OE19 with an IC50 value of 5.50 μM.

No abstract available

Fungi generate different metabolites some of which are intrinsically bioactive and could therefore serve as templates for drug development. In the current study, six endophytic fungi namely Aspergillus flavus, Aspergillus tubigenesis, Aspergillus oryzae, Penicillium oxalicum, Aspergillus niger, and Aspergillus brasiliensis were isolated and identified from the medicinal plant, Silybum marianum. These endophytic fungi were identified through intra transcribed sequence (ITS) gene sequencing. The bioactive potentials of fungal extracts were investigated using several bioassays such as antibacterial activity by well-diffusion, MIC, MBC, anti-biofilm, antioxidant, and haemolysis. The Pseudomonas aeruginosa PAO1 was used to determine the antibiofilm activity. The ethyl acetate extract of Aspergillus flavus showed strong to moderate efficacy against Staphylococcus aureus, Escherichia coli, P. aeruginosa, and Bacillus spizizenii. Aspergillus flavus and Aspergillus brasiliensis exhibited significant antibiofilm activity with IC50 at 4.02 and 3.63 mg/ml, while A. flavus exhibited maximum antioxidant activity of 50.8%. Based on HPLC, LC-MS, and NMR experiments kojic acid (1) and carbamic acid (methylene-4, 1-phenylene) bis-dimethyl ester (2) were identified from A. flavus. Kojic acid exhibited DPPH free radical scavenging activity with an IC50 value of 99.3 μg/ml and moderate activity against ovarian teratocarcinoma (CH1), colon carcinoma (SW480), and non-small cell lung cancer (A549) cell lines. These findings suggest that endophytic fungi are able to produce promising bioactive compounds which deserve further investigation.

A total of 46 endophytic fungi were isolated from Huperzia serrata and then cultured in a standard liquid medium and PDB medium. Cytotoxicity and antimicrobial activity assays revealed that seven crude extracts exhibited significant inhibitory effects on MCF‐7 and SH‐SY5Y cell lines; four crude extracts effectively inhibited the growth of Candida albicans, and 12 crude extracts demonstrated potent inhibition effects on Staphylococcus aureus. Strains displaying antimicrobial activity or potential for producing novel metabolites were selected for identification. In total, 14 strains representing 7 genera were identified, 5 of which had not been previously documented regarding their secondary metabolites. A fungus, Penicillium panissanguineum SZSS 4‐2‐2 was preliminarily selected for further chemical investigation. From the fermentation extract of P. panissanguineum SZSS 4‐2‐2, one new compound (1), one new natural product (2), and two known compounds (3 and 4) were isolated. The structures of these compounds were elucidated through spectral analysis and calculated nuclear magnetic resonance and electronic circular dichroism data. Compound 1 demonstrated a significantly stronger inhibitory effect on lipopolysaccharide‐induced nitric oxide (NO) production in RAW 264.7 macrophages, with an IC50 value of 64.91 µM. By contrast, compounds 2, 3, and 4 exhibited only moderate inhibitory effects on NO production.

No abstract available

This study reports the isolation of two natural compounds, zearalenone and hyrtiosulawesine, from the endophytic fungus Penicillium chrysogenum isolate SR192 which is associated with the invasive plant species Solanum rostratum . In general, both isolated compounds exhibited a dose-dependent stimulatory effect on the growth of four weed species when concentrations ranging from 5 to 100 µg mL-1 were tested. However, suppressive effects were observed when the concentration was increased to 500 µg mL-1, suggesting a biphasic response. Our findings indicate that these compounds have the potential to be further investigated as environment-friendly plant growth regulatory agents.

Five compounds were isolated from the fermentation broth of the oyster endophytic fungus Penicillium griseofulvum QDYM-3, including 1,6-dihydroxy-3-methoxy-8-methylxanthone (1), (+)-griseofulvin (2), (4 R,5R,6R)-4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-methyl-2-cyclohexen-1-one (3), 3-hydroxybenzyl alcohol (4), and epigriseofulvin (5). Compounds (1), (3), and (4) significantly inhibited Aβ aggregation, with compound (3) being the most effective, after the compound (3) was incubated with Aβ for 9 h, the THT fluorescence was detected to be 1089.67 AU, close to the 1044.33 AU of the positive control. Its neuroprotective effects were evaluated using an Aβ1-42 induced SH-SY5Y cell injury model, showing no cytotoxicity at concentrations of 1 to 25 µg/mL. Notably, 1 µg/mL of compound (3) reduced ROS levels by 26.87%, the enzymatic activities of SOD, CAT, and GSH were elevated by 13.97%, 20.74%, and 82.27% respectively, while the level of MDA was reduced by 20.42%. Additionally, the expression of intracellular proteins p-Akt, p-GSK-3β and β-catenin were up-regulated by 57.9%, 50.8% and 40.4%, respectively, at a sample concentration of 5 μg/ml compared with the injury group.

Abstract Penicillium macrosclerotiorum was isolated for the first time from the leaves of Ilex pubescens Hook. et Arn (VSN-2022-03-18-001) and found to produce bioactive compounds. Seven compounds were obtained from the fermentation broth and mycelia of P. macrosclerotiorum and identified as palmitic acid (1), methyl 6-acetyl-5,7,8-trihydroxy-4-methoxy-2-naphthoate (2), ergosterol (3), daidzein (4), oleuropein (5), pedunculoside (6) and acteoside (7). Compounds 3, 4 and 7 exhibited antioxidant activity against diphenyl picryl hydrazinyl with IC50 values of 58.06, 2.58 and 12.01 µg/mL, respectively. Compounds 3, 5 and 7 exhibit inhibitory activity against Escherichia coli with MIC values of 0.78, 3.13 and 3.13 mg/mL, while compounds 2, 3, 4, 5, 6 and 7 exhibited inhibitory effect on Candida albicans with MIC values of 0.20, 0.20, 0.39, 0.63, 0.78 and 0.78 mg/mL, respectively. Furthermore, Compound 4 effectively inhibited HepG2 cells, showing an IC50 of 34.03 μg/mL.

Objective To study the compounds isolated from Penicillium HDS-Z-1E, an endophytic fungal strain isolated from Taxus cuspidata and their activation effect of catalase (CAT). Methods The chemical constituents were isolated from Penicillium HDS-Z-1E, by using silica gel, Sephadex LH-20 and HPLC. The structural elucidations of five metabolites were elucidated on the basis of spectroscopic including 1H-NMR, 13C-NMR, HMBC and HSQC. Their activation sites of catalase have been investigated by molecular docking. Results Five metabolites, compounds (1–5) were isolated from Penicillium HDS-Z-1E and identified as 4-hydroxy-4-methyltetrahydro-2H-pyran-2-one (1), 4-hydroxymethyl-5, 6-dihydro-pyran-2-one (2), 5, 6-dihydro-2-oxo-2H-pyran-4-carboxylic (3), N-acetyl-hydrazinobenzoic acid (4), and methyl 2-(2, 5-dihydroxyphenyl) acetate (5). Conclusion Compound 3 is a new compound. Compounds 3 and 4 may have potential activators of catalase, providing a theoretical basis for the development of CAT activators.

Kalanchoe, as Cocor Bebek, is a genus of plants that is often used in traditional medicine because it has various biological activities, one of which is as an antioxidant. The development of research was carried out on the secondary metabolites compounds of endophytic fungi from the stem of K. millotii as the Cocor Bebek species. Endophytic fungi are microorganisms that live in plant tissues, generally producing secondary metabolites that have bioactivities such as anticancer, antioxidant, and antibacterial. One of the endophytic fungi isolated from the stem of K. millotii was identified as Penicillium citrinum. The potential antioxidant activity of the secondary metabolites contained in the ethyl acetate extract of the endophytic fungus P. citrinum is interesting to study. The sample extract was extracted using non-polar, semi-polar, and polar solvents. The ethyl acetate extract was separated and purified by various chromatographic methods to obtain 8 mg compound 1, as a yellow solid. The chemical structure was determined by spectroscopic methods. Based on spectrum analysis of 1D-NMR, 2D-NMR, FTIR, and UV-Vis, compound 1 was identified as 4-(2-ethylbutoxy)-3,5-dimethoxybenzaldehyde. Antioxidant activity testing of ethyl acetate extract and compound 1 was carried out using the DPPH (2,2-diphenyl-1-pikrilhidrazyl) method. The test results on the extract showed weak activity with an IC50 value of 401.01 ppm while compound 1 showed moderate activity with an IC50 value of 221.41 ppm

BACKGROUND An endophytic fungal strain Penicillium crustosum was isolated from the seagrass Posidonia oceanica and investigated to identify its antimicrobial constituents and characterize its metabolome composition. The ethyl acetate extract of this fungus exhibited antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) as well as an anti-quorum sensing effect against Pseudomonas aeruginosa. METHODS The crude extract was profiled by UHPLC-HRMS/MS and the dereplication was assisted by feature-based molecular networking. As a result, more than twenty compounds were annotated in this fungus. To rapidly identify the active compounds, the enriched extract was fractionated by semi-preparative HPLC-UV applying a chromatographic gradient transfer and dry load sample introduction to maximise resolution. The collected fractions were profiled by 1H-NMR and UHPLC-HRMS. RESULTS The use of molecular networking-assisted UHPLC-HRMS/MS dereplication allowed preliminary identification of over 20 compounds present in the ethyl acetate extract of P. crustosum. The chromatographic approach significantly accelerated the isolation of the majority of compounds present in the active extract. The one-step fractionation allowed the isolation and identification of eight compounds (1-8). CONCLUSION This study led to the unambiguous identification of eight known secondary metabolites as well as the determination of their antibacterial properties.

Abstract The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus Penicillium sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3S,4R)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2H)-one (1), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2H)-one (2), decaturin B (3), 15-hydroxydecaturin A (4), oxalicine A (5), pileotin A (6), pyrandecarurin A (7), decaturenol A (8), decaturenoid (9), penisarins A (10), oxaline (11), (4E,8E)-N-D-2'-hydroxyocta-decanoyl-1-O-β-D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (12), ergosterol (13) and stigma-5-en-3-O-β-glucoside (14), were separated. Among the known compounds, 2, 7, 12 and 14 were not found in our previous research on this strain. The structure of the new compound was identified by spectroscopic techniques such as HR-ESIMS, 1D NMR, 2D NMR and CD. Furthermore, all the isolated compounds were tested for their antimicrobial activities, and only compounds 1, 2 and 11 showed weak activities against S. aureus, with MICs of 128 μg/mL. Graphical Abstract

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Eight previously undescribed specialized metabolites were obtained and characterised from Penicillium griseofulvum, a root endophyte from Delphinium grandiflorum, namely three aryl ether derivatives (1-3), three 2,5-DKP derivatives (7-9), two aryl esters (10-11), along with 22 known compounds. Their structures were fully characterised by comprehensive spectroscopic analyses. Notably, compounds 25, 28, and 30 exhibited moderate cytotoxic activities against triple-negative breast cancer (TNBC) cells (MDA-MB-231). Compound 29 demonstrated potent broad-spectrum antibacterial activity against clinical drug-resistant bacteria.

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Introduction Endophytic fungi associated with medicinal plants have proven to possess a high potential to produce structurally diverse metabolites, some of which are valuable for medicinal applications. In this study, Penicillium sp. YT2019-3321, an endophytic fungus derived from traditional Chinese medicine Lonicera japonica, was chemically studied. Methods The chemical structures of the isolated compounds were established by a correlative interpretation of HRESIMS and NMR spectroscopic data. The optical resolution of (±)-1 by chiral HPLC yielded individual enantiomers (+)-1 and (–)-1, and their stereochemistry were solved by X-ray diffraction crystallography, respectively. Results and discussion Eight structurally diversified secondary metabolites, including two previously unreported polyketides, named (±)-chrysoalide B (1) and penicidone E (2), were isolated and identified from Penicillium sp. YT2019-3321. Compound 2 possessed the γ-pyridone nucleus, which is rarely found in natural products. Cytotoxic assay revealed that the new compound 2 demonstrated a dose-dependent cytotoxicity against the human pancreatic tumor cells PATU8988T with the IC50 value of 11.4 μM. Further studies indicated that 2 significantly induced apoptosis of PATU8988T cell lines, characterized by the morphologies abnormity, the reduction of cell number, the upregulation of proportion of apoptotic cells, and the ratio of Bcl-2 to Bax. Our study demonstrates that fungal secondary metabolites may have important significance in the discovery of drug leads.

Abstract Endophytic fungi are the plant symbiont with highly diverse nature and poorly defined ecological importance in host fitness. Although there are the reports on the isolation and characterization of fungal endophytes from a variety of hosts, there is still no report of Penicillium citrinum from Azadirachta indica. In this study, an endophytic P. citrinum was isolated from A. indica. The purified fraction of secondary metabolites was characterized by combining TLC, GC-MS, 1H NMR and 13C NMR analyses. The TLC purified fraction was identified as milbemycin. The pure fraction did not show any antioxidant activity while crude extract showed strong antioxidant activity (DPPH inhibition capacity; IC50 = 52.13 μg ml−1). The secondary metabolites displayed significant antimicrobial activity against human's pathogenic bacteria and fungi. The inhibition zones between 15 and 20 mm were recorded against Gram +ve Staphylococcus aureus, Enterococcus faecalis and Gram–ve Aeromonas hydrophila, while maximum inhibition of 29 mm was observed against Trichophyton mentagrophytes. P. citrinum can be a promising fungus that has broad spectrum antimicrobial activity and may provide future insight towards the production of bioactive compounds.

Abstract Twenty-two metabolites were isolated from Penicillium sp. CPCC 401423 cultured on rice. The structures of all compounds were elucidated mainly by MS and NMR analysis as well as the necessary CD experimental evidence, of which penicillidione A (1), penicillidione B (2), (E)-4-[(4-acetoxy-3-methyl-2-butenyl)oxy]phenylacetic acid (3), (S)-2-hydroxy-2-{4-[(3-methyl-2-butenyl)oxy]phenyl} (4), (S)-4-(2,3-dihydroxy-3-methyl-butoxy)phenylacetic acid (5), (E)-4-[(3-carboxy-2-butenyl)oxy]benzoic acid (6), (Z)-4-[(4-hydroxy-3-methyl-2-butenyl)oxy]benzoic acid (7), open-cycled N-demethylmelearoride A (12), and penostatin M (16) were identified as new compounds. The cytotoxic activity against human pancreatic carcinoma cell line MIA PaCa-2a was detected. Among them, compounds 13–15 and 22 displayed significant cytotoxicity against MIA-PaCa-2 cells with IC50 values of 8.9, 36.5, 31.8, and 22.3 µM, respectively (positive control gemcitabine IC50 65.0 µM). Graphical Abstract

Chemical study of the fermentation culture of the marine‐derived fungal strain Penicillium sp. OPR23‐FS02 led to isolation of ten secondary metabolites, including two terpenes, purpuride (1) and penioxalicin (2) and eight polyketides, trans‐3,4‐dihydro‐3,4,8‐trihydroxynaphthalen‐1(2H)‐one (3), chloromonilinic acid B (4), chrysophanol (5), emodin (6), ω‐hydroxyemodin (7), questin (8), endocrocin (9), and ergochrome F (10). Their structures were elucidated by analyzing their NMR and HRESI mass spectra and comparing with the literature data. Compound 9 was weakly cytotoxic against HepG2 cell line, with an IC50 value of 89.86 ± 2.63 µm. Compounds 4 and 10 showed antimicrobial effect against Enterococcus faecalis whereas 6 inhibited Bacillus cereus growth, with the same MIC values of 64 µm.

Macrozamia communis and its associated endophytic fungi are untapped sources of bioactive metabolites with great potential for medicinal exploitation. Chemical investigation of the mycelial extract derived from an endophytic fungus Penicillium sp. MNP-HS-2 associated with M. communis fruit afforded four mycophenolic acid derivatives recognized as previously undescribed natural products (1-4), together with nine known metabolites (5-13). Chemical structures of isolated compounds were determined based on extensive spectroscopic analyses, including 1D/2D NMR and HRESIMS. The absolute stereochemistry of alternatain E (1) was unambiguously established by comparing its experimental and calculated time-dependent density functional theory electronic circular dichroism spectra (TDDFT-ECD). All isolated compounds were assessed for their antimicrobial and cytotoxic activities, where mycophenolic acid methyl ester (7), displayed significant cytotoxic activity against seven different cell lines with IC50 values in the low micromolar to nanomolar range. Mycophenolene A (3) exhibited significant antibacterial activity against Staphylococcus aureus (MIC = 2.1 μg/mL).

Chemical investigation of the sesame-associated fungal strain Penicillium hetheringtonii IMBC-NMTP04 resulted in isolation of five compounds, penicitrinone A (1), dihydrocitrinin (2), janthinone (3), coniochaetone B (4), and 9-oxo-10(E),12(E)-octadecadienoic acid (5). Their chemical structures were elucidated by spectroscopic methods, including 1D and 2D NMR and mass spectra in comparison with the literature data. Compound 1 showed modest cytotoxicity toward LNCaP, HepG2, MCF-7, KB, SK-Mel-2, and HL-60 human cancer cell lines, with IC50 values ranging from 60.1 to 84.2 mM while 5 was cytotoxic toward only HL-60 cell line (IC50 = 71.6 mM). All the compounds significantly inhibited E. faecalis, S. enterica, and C. albicans growth, with MIC values ranging from 12.5 to 50.0 mM. Compounds 2, 4, and 5 suppressed the growth of B. cereus, while both 1 and 2 showed antimicrobial effect against E. coli, with the same MIC value of 200 mM. This is the first time to report the chemical constituents of Penicillium hetheringtonii and the antimicrobial effect of 2–4.

This study was to investigate the cytotoxic and antimicrobial activities of ethyl acetate extract yielded from fermented fungi Trichoderma reesei strain: JCM 2267, Aspergillus flavus strain MC-10-L, Penicillium sp, and Aspergillus fumigatus associated with Stylissa flabelliformis sponge, and also to investigate the significant component in ethyl acetate extract of it. Antimicrobial experimentation was performed to various microbes with liquid microdilution method. The assessment of antimicrobials was undertaken by observing the value of MIC50. Cytotoxic testing was performed using MTT assay method. The cytotoxic activity evaluation was conducted by finding the value of IC50. The compound analysis in the ethyl acetate extract was used GC-MS. The result showed that in the antimicrobial experimentation, there was a variation in the percentage of inhibition where the smallest MIC50 values were found in Aspergillus fumigatus fungi ethyl acetate extract against Candida albicans ATCC 10231 at 1.3g/mL. The result of the cytotoxic test against tumor cell line T47D, the lowest IC50 was found in Penicillium sp fungi with 111g/mL value. Aspergillus flavus strain MC-10-L fungi, Penicillium sp, and Aspergillus fumigatus obtained from sponge isolation Stylissa flabelliformis have antimicrobial and cytotoxic activity with various range. All fungi extracts are not toxic against normal cells (Vero cells). The class of compounds in ethyl acetate fungi extract Trichoderma reesei strain JCM 2267 are mostly cyclohexane.

The organic extract of liquid cultures of the marine-derived Penicillium sp. was investigated. Fractionation of the extracts of the fungus led to the purification and identification of two new compounds, penicillatides A (1) and B (2), together with the previously reported cyclo(R-Pro–S-Phe) (3) and cyclo(R-Pro–R-Phe) (4). The structures of compounds 1–4 were assigned by extensive interpretation of their NMR and high-resolution mass spectrometry (HRMS). The antiproliferative and cytotoxic activities of the compounds against three human cancer cell lines as well as their antimicrobial activity against several pathogens were evaluated. Compounds 2–4 displayed variable cytotoxic and antimicrobial activities.

In the present study, we reported eight endophytic fungi isolated from stems, rhizomes, and roots of red ginger (Zingiber officinale var. rubrum), collected from Bali, Indonesia. Molecular biology protocol through amplification of internal transcribed spacer and LSU region led to the identification of six fungal isolates as Microdochium colombiense ZOR-S1-1, Phlebiopsis flavidoalba ZOR-S1-3, Penicillium citrinum ZOR-S1-4.1, Dactylonectria anthuriicola ZOR-Rh1-3, Setophoma terrestris ZOR-Br1-1, and Xylaria cubensis ZOR-Rh1-1. Meanwhile, two fungal isolates, ZOR-S1-4 and ZOR-Br1-2, are remain unidentified. Following rice fermentation of all isolated endophytes, all fungal extracts were subjected to antimicrobial, toxicity, and cytotoxicity assays. In the antimicrobial assay, S. terrestris ZOR-Br1-1 extract showed the most pronounced activity against Staphylococcus aureus ATCC 6538 and Candida albicans ATCC 10231, with MIC values of 31.3 and 15.6 μg/ml. Meanwhile, D. anthuriicola ZOR-Rh1-3 extract revealed the most potent activity in toxicity screening employing the brine shrimp lethality test (BSLT), with an LC50 value of 6.8 μg/ml. When tested further for cytotoxicity against breast cancer cells, MCF-7 and 4T1, extracts of D. anthuriicola ZOR-Rh1-3, P. citrinum ZOR-S1-4.1, unidentified isolates ZOR-S1-4 and ZOR-Br1-2, showed strong to moderate inhibition against both tested cell lines with IC50 values ranging from 14 to 74 μg/ml. In light of the bioactivity of endophytic fungal extracts from red ginger found in this study, investigation on secondary metabolites and their pharmacological action on antimicrobial and cytotoxicity of endophytic S. terrestris ZOR-Br1-1, D. anthuriicola ZOR-Rh1-3, and P. citrinum ZOR-S1-4.1 are of scientific interest for further research. Moreover, this result highlights the bioprospecting opportunity of endophytic fungi associated with medicinal plants as a source of bioactive secondary metabolites.

A chemical investigation on the marine-derived fungus Penicillium crustosum SCNU-F0046 resulted in the isolation and characterization of four new benzofurans (1, 2, 5, 6) and four known analogues (3, 4, 7, 8). Their structures were elucidated by a combination of mass, NMR spectroscopy, electronic circular dichroism (ECD) calculations and X-ray crystallographic analyses. The antimicrobial experiments disclosed compound 1 exhibited moderate antibacterial activity, while compound 6 showed antifungal activity. In addition, the anti-inflammatory activity of aza-benzofuran compounds (1–4) was also evaluated. Bioassays revealed that compounds 1 and 4 exhibited anti-inflammatory activity by inhibiting nitric oxide release without cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages with IC50 values of 17.3 and 16.5 μM, respectively. The docking study revealed that compounds 1 and 4 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds.

Marine associated fungi were isolated from marine sponges collected at two ecologically distinct localities in Hurghada. Macroscopic characteristics were employed to identify and classify distinct fungal strains using ethanol-hypochlorite surface sterilization. The fungal isolates, identified as marine fungi, were cultivated on Egyptian white rice media to yield bioactive crude extracts following ethyl acetate extraction. The most potent isolate was strain DI7S9. This strain, morphologically and genetically identified as Penicillium rubens (GenBank: OP709283.1), was extensively fermented to yield biomass for subsequent experiments. The primary component of the extract was trans-9-octadecenoic acid, pentyl ester, as determined by GC-MS analysis. According to SwissADME, this compound exhibits moderate drug-likeness, limited gastrointestinal absorption, and low permeability across the blood-brain barrier. The crude extracts exhibited selective cytotoxicity, effectively inhibiting malignant HCT-116 and A-498 cells at low IC₅₀ values (30.44 and 37.99 µg/mL), while inflicting minimal damage on normal HEK-293 cells (IC₅₀ = 77.89 µg/mL). Notable suppression of E. coli, S. aureus, A. niger, and C. albicans was observed. The metabolites of P. rubens DI7S9 exhibit significant pharmacological potential, warranting further investigation into their mechanisms of action and potential therapeutic applications. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12866-026-04962-4.

The fungi are sponge symbionts.  The fungus Penicillium nalgiovense acc MK087096  is a symbiont of the sponge Gelliodes fibulata. This symbiont has antibacterial activity, which supports the development of sponge-based drugs that are as effective as antibiotics. However, the primary challenge in developing marine resource-based medicine is the availability and sustainability of sponge raw materials. Fermentation biotechnology using sponge symbiont fumgi is an effective solution to address these challenges, as it allows the production of bioactive secondary metabolite compounds in large quantities, which can be used as raw materials for pharmaceutical preparation. The aim of this study was to determine the optimal medium and fermentation duration for producing secondary metabolites with antibiotic properties from the symbiotic fungus Penicillium nalgiovense, isolated from the sponge Gelliodes fibulata. This study was conducted naturally. The symbiotic fungus from the sponge Gelliodes fibulata was cultivated to facilitate growth. Fermentation was conducted with variations in secondary metabolite harvesting times of 2, 4, 6, 8, 10, and 12 days.  Secondary metabolites were obstained using liquid-liquid extraction with ethyl acetate. The optimal medium and fermentation time were determined based on the yield percentage for each medium across the six time variations. The fermentation biotechnology of the symbiotic fungus Penicillium nalgiovense acc MK087096 from the spone Gelliodes fibulata was carried out on SDB, PDB, also coconut flake-enriched PDB media.  The results showed the growth of the fungus and the production of bioactive secondary metabolites with antibiotic properties ...

Recently, the demand for fungal pigments has increased due to their several benefits over synthetic dyes. Many species of fungi are known to produce pigments and a large number of fungal strains for pigment production are yet to be extensively investigated. The natural pigment from sustainable natural sources has good economic and industrial value. Many synthetic colorants used in textile and various industries have many harmful effects on the human population and environment. Pigments and coloring agents may be extracted from a wide range of fungal species. These compounds are among the natural compounds having the most significant promise for medicinal, culinary, cosmetics, and textile applications. This study attempts to isolate and optimize the fermentation conditions of Penicillium sclerotiorum strain AK‐1 for pigment production. A dark yellow‐colored pigment was isolated from the strain with significant extractive value and antioxidant capacity. This study also identifies that the pigment does not have any cytotoxic effect and is multicomponent. The pigment production was optimized for the parameters such as pH, temperature, carbon and nitrogen source. Fabric dyeing experiments showed significant dyeing capacity of the pigment on cotton fabrics. Accordingly, the natural dye isolated from P. sclerotiorum strain AK‐1 has a high potential for industrial‐scale dyeing of cotton materials.

Endophytic fungi are well recognized as prolific producers of structurally diverse natural products. In this study, three endophytic fungal isolates − Penicillium singorense MA‐S1, MA‐S3, and PDA‐S2 – were obtained in Sasmuan mangrove forest, which had previously been affected and altered by the lahar from the 1991 eruption of Mt. Pinatubo. Morphological characterization and 18S rDNA/ITS sequencing confirmed their taxonomic placement in the Penicillium genus. The three isolates were subjected to fermentation using rice medium, and metabolites were extracted using ethyl acetate. Crude extracts were then fractionated using the modified Kupchan method, followed by solid‐phase extraction (SPE). Disc diffusion assays indicated that the dichloromethane and methanol fractions, as well as the 25% and 100% methanol SPE fractions, exhibited the highest zone of inhibition (ZOI) against the clinical isolates, surpassing the ZOI of voriconazole. Liquid chromatography‐tandem mass spectrometry analysis of the fractions, combined with Global Natural Products Social (GNPS) molecular networking, putatively identified the presence of known bioactive metabolites, including diketopiperazines, peptides, and terpenes. Furthermore, other clusters in the network lacked spectral matches in the GNPS library, suggesting the presence of putatively novel metabolites in the extracts. Overall, the study highlights the potential of endophytic fungi from a post‐volcanic mangrove ecosystem as valuable sources of bioactive natural products.

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In this study, a biomembrane surface fermentation was used to produce red pigments of Penicillium novae-zelandiae, and the significant improvement in pigment production by the addition of 0.4 g/L of tyrosine demonstrated that the red pigments probably contained betalain. Therefore, one red pigment was purified, and identified as 2-decarboxybetanin by high-resolution mass spectrometry (MS) and MS/MS analysis. Transcriptomic analysis revealed the differentially expressed genes and metabolic profile of P. novae-zelandiae in response to different cultivations and exhibited the complete biosynthetic pathway of 2-decarboxybetanin in P. novae-zelandiae. Betalains are important water-soluble nitrogen-containing food coloring agents, obtained mainly from beetroot by chemical extraction. This paper is the first report about the production of betalain by microbial fermentation, and results exhibit the possible use of fungal fermentation in future 2-decarboxybetanin production.

ABSTRACT Oncomelania hupensis, the sole intermediate host for Schistosoma japonicum, is a barrier to schistosomiasis elimination. Currently, chemical molluscicides are widely used; however, they can lead to environmental residues and toxicity problems. Molluscicides derived from microorganisms offer the advantages of mass production and environmental compatibility. Building on the molluscicidal activity of Penicillium aurantiocandidum Z12, we fractionated its fermentation broth via centrifugation and solvent extraction to identify active components. Ethyl acetate extract (EAE) and n-butanol extract (BE) demonstrated molluscicidal effects in toxicity tests. EAE (LC50 = 1.40 g/L, 95% Cl = 1.21-1.60; LC90 = 2.92 g/L, 95% Cl = 2.44-3.78) was significantly more potent than BE (LC50 = 2.17 g/L, 95% Cl = 1.96-2.39; LC90 = 3.31 g/L, 95% Cl = 2.93-4.07). ANOVA/Kruskal–Wallis analysis showed specific concentrations of EAE (0.4, 0.7 g/L) and BE (3.2 g/L) significantly reduced snails’ total hepatic protein content after 72 h. Treatment with EAE and BE at LC50 values also significantly suppressed superoxide dismutase (SOD) and peroxidase (POD) activities in head-foot tissue after 72 h. In conclusion, molluscicidal components concentrate in EAE and BE. Their mechanism involves inhibiting hepatic protein synthesis and suppressing SOD/POD activity, leading to snail death. More research is needed to further explore the specific effective constituents and their mechanisms.

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is a global health concern, necessitating the development of new antibacterial drug. Marine natural products (MNPs) with unique structures and significant activities are underexploited sources for the discovery of new antibacterial lead compounds. However, the systematic review focusing on MNPs with anti-MRSA activity is still scarce. This review firstly summarized the anti-MRSA MNPs, including their geographical origin, chemical structures and biological activities, reported from 2014 to July 2025. For a better understanding, these 269 MNPs mainly including polyketides and alkaloids are classified and presented according to their biological origins (marine microorganisms, animals and plants). The preliminary structure-activity relationship and the mechanisms of action of some promising MNPs are also discussed. We found that marine microorganisms of the genera Streptomyces, Penicillium and Aspergillus and the animal sponges were the predominant producers of anti-MRSA MNPs. Strikingly, 80 compounds exhibited more potent anti-MRSA activity than that of the positive control or comparable to that of the positive control. This review highlights the huge potential of MNPs as scaffolds for developing next-generation antibacterial agents to combat MRSA and will inspire the development of novel marine drugs.

Marine-derived fungi have shown great potential for discovering new bioactive secondary metabolites. The fungus strain Penicillium chrysogenum BTBU20212025 was fermented at 28°C for 30 days under static conditions using a rice medium. Then, the extract of the fermented materials was subjected to chromatography to yield compounds 1-9. The chemical structures of the isolated compounds were determined by comprehensive analysis of 1D and 2D NMR and high-resolution mass spectrometry. Additionally, the antibacterial activity was performed in a 96-well plate format using the microdilution method in an MHB broth medium. A new natural diketopiperazine derivative, 12-hydroxy-cyclo-(L-tryptophyl-L-phenylalanyl) (1), along with eight known compounds, including cyclo-(L-tryptophyl-L-phenylalanyl) (2), haenamindole (3), meleagrin (4), citreohybridonol (5), 1,3,6-trihydroxy-7-(1',2'-dihydroxypropan-2-yl)- anthraquinone (6), citreoisocoumarinol (7), penicillocitrin A (8), and methyl 2-(2,6- dihydroxybenzoyl)-3-hydroxy-5-(hydroxymethyl)benzoate (9), was identified from Penicillium chrysogenum BTBU20212025. Compounds 4, 6, and 8 exhibited inhibitory effects against Staphylococcus aureus with a minimum inhibitory concentration value of 50 μg/mL. Optical rotations were measured by an Anton Paar MCP 200 Modular Circular polarimeter. NMR spectra were reordered on a Bruker Avance 500 MHz spectrometer at 25 °C with solvent residue as references. HRESIMS was measured by using Waters G2-XS QTOF mass spectrometer. Column chromatography was performed on normal phase silica gel (thin layer chromatography H silica) and Sephadex LH-20. Semi-preparative high performance liquid chromatography (HPLC) was performed on an Agilent 1260 instrument with a diode array detector by using Agilent Eclipse XDB-C8 column (250 × 9.4 mm, 5 um) at 28 °C. The marine-derived fungus strain Penicillium chrysogenum BTBU20212025 showed potential for producing new and antibacterial natural products.

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A new pyrazine derivative, trypilepyrazinol (1), a new α-pyrone polyketide, (+)-neocitreoviridin (2), and a new ergostane analogue, 3β-hydroxyergosta-8,14,24(28)-trien-7-one (3), were isolated and characterized along with five known compounds from the marine-derived fungus Penicillium sp. IMB17-046. The structures of these new compounds were determined using spectroscopic data analyses (HRESIMS, 1D- and 2D-NMR), X-ray crystallography analysis, and TDDFT ECD calculation. Compounds 1 and 3 exhibited broad-spectrum antiviral activities against different types of viruses, including human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza A virus (IAV), with IC50 values ranging from 0.5 to 7.7 μM. Compounds 1 and 2 showed antibacterial activities against Helicobacter pylori, a causative pathogen of various gastric diseases, with minimum inhibitory concentration (MIC) values of 1–16 μg/mL.

Six new aurovertins (1-6) and a new citreoviridin derivative (7), together with six known analogues (8-13), were isolated from the marine-derived Penicillium sp. OUCMDZ-5930. Their structures were determined based on detailed spectroscopic analysis and ECD calculations. The putative nonenzymatic formation from citreoviridin to various aurovertins was presented, which was confirmed by chemical transformations. These results provide new insights into the formation mechanism of the 2,6-dioxabicyclo[3.2.1]octane ring system present in aurovertin-type natural products.

Fungal secondary metabolites (SMs) are complex organic compounds comprising a variety of biological activities that are essential in medicine. These natural products can be found in various environments, with studies demonstrating the importance of studying marine-sourced fungi due to the increased potency of the compounds they produce. In this study, we sourced a Penicillium rubens YAP001 strain isolated from Exaiptasia diaphana and explored an avenue for the upregulation of its SMs by combining the one-strain-many-compounds (OSMAC) strategy with genetic manipulation of negative global regulator of secondary metabolism, mcrA. Here, we generated a mcrAΔ strain of marine P. rubens (YAP001), which led to the detection of sorbicillinoids, which is significant due to the prior discovery that these compounds illicit cytotoxic effects that have the potential as an anticancer agent. Specifically, we found that sorbicillin was not only upregulated but the mutant strain also produced the dimeric product, trichodimerol, which often exhibits stronger biological activities compared to sorbicillin. Furthermore, the reduced form of trichodimerol, dihydrotrichodimerol, was also detected in the mutant strain. This work suggests that genetic manipulation of global regulators in combination with the OSMAC method in filamentous fungi is a promising technique for upregulating pathways of interest for small-molecule drug discovery.

Marine-derived endophytic fungi are a rich source of structurally unique and bioactive natural products. In this study, we isolated a new isochromane derivative, (6S,7R)-7-methoxy-10,11,12,13-tetramethylisochromane-1,3-diol (compound 1), along with seven known compounds (compounds 2-8), from Penicillium sp. Fx1.1.3, an endophyte obtained from the stem of Tetragonia tetragonioides collected in Beigong Island, China. Structural elucidation of compound 1 was performed by 1D and 2D NMR, HR-ESI-MS, and ECD spectral analyses, confirming its absolute configuration as 6S,7R. Antimicrobial screening showed that compound 1 exhibited moderate inhibitory activity 125 μg/mL (494 µM) against Staphylococcus aureus, Escherichia coli, and Candida albicans, while compounds 2 and 4 showed more potent inhibitory activity 31.25 μg/mL or 125 µM and 82 µM, respectively against S. aureus. In addition, compounds 1 and 6 displayed significant antiviral activity against A/Puerto Rico/8/34 (H1N1) virus with IC50 values of 8.99 ± 3.32 and 4.04 ± 1.10 μg/mL (35.52 ± 13.12 and 11.40 ± 3.10 μM), respectively.

Obesity has become a worldwide health problem. Seeking natural products with anti-obesity activity from lots of fungi has drawn the attention of pharmacologists. In our study, dipenipenoids A and B (1 and 2), the first dimeric indole-diterpenoids with a rare C-20–C-22′ linkage, and their monomers (3 and 4), were isolated from a marine-derived Penicillium sp. CF-06 fungus from Suaeda salsa. The absolute configurations of 1–3 were assigned by the calculated TDDFT ECD method. The structure of 4 was verified by a single-crystal X-ray diffraction method for the first time. Interestingly, 1 and 2 displayed significant effects on the differentiation of 3T3-L1 adipocytes by down-regulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) proteins, while monomers 3 and 4 exhibited no activity. Molecular docking results explained the mechanism that the interaction between dimer 1 and PPARγ was stronger than that between monomer 3 and PPARγ. Our research could provide new insight for the discovery of anti-obesity drugs.

Marine-derived Penicillium fungus gained significant attention in recent years due to their potential as a valuable source of unique natural compounds with a wide range of chemical structures and bioactive capabilities. The primary origins of marine-derived Penicillium fungi are mangroves, sediments, marine shrimps, corals, starfish, algae, and sponges. A total of 390 unique natural compounds were extracted from Penicillium fungi which were found in marine environments. These compounds primarily consist of polyketides, alkaloids, terpenoids, chromone derivatives, anthraquinones, citrinins, steroids, azaphilones, and macrolides. Biological studies demonstrated that these compounds exhibit antimicrobial, anti-inflammatory, cytotoxic, pesticide development, neuroprotective, anti-glioma, anti-proliferative, α-glucosidase inhibitory activities, anti-allergic, photo-protective, anti-angiogenic effect, larvicidal activity, antiviral, anti-diabetic activity, and other activities that could be useful in the development of new drugs. This study shed the light on the recent discovery of bioactive MNPs (marine-derived Penicillium; natural products) derived from Penicillium fungi found in marine environments in the last five years from 2020 to 2025, classified the MNPs based on the sources of the fungi and their specific biological activities. Besides, the results of molecular docking studies recently performed on Penicillium metabolites referring to various biological activities were also compiled in this review. Thus, this review highlighted that Penicillium species obtained from marine organisms act as an everlasting mine of bioactive novel metabolites combating various ailments.

Marine-derived filamentous fungi are a rich source of structurally diverse and biologically active natural products. However, many biosynthetic gene clusters (BGCs) in fungi remain silent under standard conditions. In this study, we employed a metabolic shunting strategy to disrupt azaphilone biosynthesis in the marine-derived fungus Penicillium sclerotiorum E23Y-1A by deleting the pathway-specific regulator gene A00667. HPLC analysis revealed the emergence of new metabolite peaks in the mutant strain Δ667 compared to the wild type. Subsequent purification yielded seven compounds: the mutant produced two novel meroterpenoids sclerotilins A and B (1 and 2) along with the known steroids ergosta-5,7,22-trien-3β-ol (3) and cerevisterol (4), while the wild type yielded the known steroid (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (5) and two azaphilones geumsanol G (6) and 5-chloro-3-[(1E,3R,4R,5S)-3,4-dihydroxy-3,5-dimethyl-1-hepten-1-yl]-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-(7R,8R,8aS)-6H-2-benzopyran-6-one (7). Bioactivity assays showed that compound 6 exhibited moderate antimicrobial activity against Staphylococcus aureus, and compound 3 displayed moderate cytotoxicity against five human cancer cell lines. These results demonstrate that A00667 is essential for azaphilone biosynthesis and that its disruption leads to the production of structurally distinct natural products, highlighting the potential of pathway engineering to redirect fungal metabolism to yield novel natural products.

Marine-associated polar fungi are promising sources of structurally diverse natural products. To investigate polyketide metabolites from the Antarctic moss-derived fungus Penicillium sp. OUCMDZ-4014, HSQC NMR combined with DeepSAT analysis was used to prioritize fractions enriched in cyclic and aromatic polyketides, and chromane-like metabolites. Chromatographic separation yielded ten resorcylic acid lactone-derived aromatic polyketides, including RAL macrolides, ring-opened esters, and isocoumarins, among which compounds 4–7 were new. Their planar structures were established by HRESIMS and 1D/2D NMR analyses. Their chemical structures including configurations were established by HRESIMS, 1D/2D NMR, ECD calculations, 13C NMR calculations, and DP4+ analysis. Isocoumarins 7–10 displayed diverse levels of α-glucosidase inhibition, with compound 9 being the most active (IC50 = 47.0 ± 3.83 μM). Kinetic analysis indicated noncompetitive inhibition by 9 and mixed-type inhibition by 10. Genome mining revealed a putative res biosynthetic gene cluster containing HR-PKS, NR-PKS, and tailoring-enzyme genes. Compound 1 underwent nonenzymatic conversion into 9 under culture-medium conditions, while trace conversion was also observed during concentration, revealing a chemical link between the RAL macrolide and isocoumarin scaffolds, and highlighting the contribution of post-biosynthetic chemical transformation to fungal polyketide diversification.

Three new, previously undescribed tanzawaic acids, steckwaic acids H–J (1–3), and twenty-three known natural products (4–26) were isolated from the marine algicolous fungus Penicillium steckii SCSIO 41040. Structurally, compound 3 underwent a rare hydration reaction at the double bond of its carboxylic acid side chain. The chemical structures and stereochemistry were determined using comprehensive spectroscopic analyses, including NMR, electronic circular dichroism (ECD) calculations, and high-resolution electrospray ionization mass spectrometry (HRESIMS), and verified by literature comparison. The protective effect of tanzawaic acids on inflammatory damage to the intestinal epithelial barrier was assessed using an LPS-stimulated Caco-2/THP-1 co-culture model. Notably, immunofluorescence and Western blotting assays showed that compound 10 significantly enhanced the fluorescence signals and protein expression of ZO-1 and occludin, alleviated lipopolysaccharide (LPS)-induced intestinal barrier damage in Caco-2 cells, and contributed to the re-establishment of intestinal barrier homeostasis. Our findings demonstrate the critical role of tanzawaic acids in maintaining intestinal barrier integrity, identifying them as promising lead compounds for UC treatment.

Diverse bioactive compounds were derived from the marine Penicillium sp. EMS8, isolated from the Mediterranean Sea, Abu Qir coast, Alexandria, Egypt. The large-scale cultivation of EMS8 on solid media led to an ethyl acetate extract with high anti-microbial activity against various pathogenic strains. The metabolomic profile of the strain extract obtained by LC-HRMS/MS analysis and dereplication, revealed the presence of 396 compounds. Subsequent data processing using MassHunter and MZmine 2.5 enabled the construction of a feature-based molecular network on the Global Natural Products Social Molecular Networking (GNPS) platform, followed by visualisation in Cytoscape. The revealed clusters of structurally related molecules, including several chlorinated compounds indicated by characteristic isotopic patterns and similar DAD spectra. The extract was then submitted to a series of chromatographic purifications resulting in a new amide derivative; methyl (E)-6-((5-methoxy-5-oxopentyl) amino)-6-oxohex-3-enoate (1), and N-acetyl tyrosine methyl ester (2), a new natural product, alongside four chlorinated azaphilone derivatives (3-6), and further eleven known compounds. The structures of isolated compounds were investigated using 1D (1H,13C), 2D (H,H COSY, HSQC, HMBC) NMR, and HR-ESIMS mass spectrometry. The results emphasise the importance of the marine fungus as a rich source of diverse bioactive compounds with high capacity as antimicrobial agent.

Five new fusarin derivatives, steckfusarins A–E (1–5), and two known natural products (6, 7), were isolated and identified from the marine algicolous fungus Penicillium steckii SCSIO 41040. The new compounds, including absolute configurations, were determined by spectroscopic analyses and calculated electronic circular dichroism (ECD). All new compounds were evaluated for their antioxidant, antibacterial, antifungal, antiviral, cytotoxic, anti-inflammatory, antioxidant, cholesterol-lowering, acetyl cholinesterase (AChE) enzyme and 6-phosphofructo-2-kinase (PFKFB3) and phosphatidylinositol-3-kinase (PI3K) inhibitory activities. The biological evaluation results revealed that compound 1 exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH), with an IC50 value of 74.5 µg/mL. In addition, compound 1 also showed weak anti-inflammatory activity at a concentration of 20 µM.

Communesins are rare alkaloids isolated from fungi of the genus Penicillium. In this work, the extract of a marine-derived Penicillium expansum strain was studied using targeted molecular networking approach allowing to detect 65 communesins including 55 novels. A fragmentation pattern for dimethylvinyl communesins was established and a script was implemented allowing to predict the structure and map all communesins in a global molecular network. A semisynthetic strategy was carried out to obtain some minor congeners from the two isolated communesins A and B. Nine communesins were then synthetised: two of them were already described as produced by the studied strain; four are new natural products which occurrence in the extracts was confirmed; three are new semi-synthetic analogues never described so far. These communesins were evaluated for their cytotoxicity on two human cancer cell lines KB and MCF-7 leading to a preliminary study of their structure-activity relationships.