The marine-derived fungal strains KMM 4718 and KMM 4747 isolated from sea urchin Scaphechinus mirabilis as a natural fungal complex were identified as Penicillium sajarovii and Aspergillus protuberus based on Internal Transcribed Spacer (ITS), partial β-tubulin (BenA), and calmodulin (CaM) molecular markers as well as an ribosomal polymerase two, subunit two (RPB2) region for KMM 4747. From the ethyl acetate extract of the co-culture, two new polyketides, sajaroketides A (1) and B (2), together with (2′S)-7-hydroxy-2-(2′-hydroxypropyl)-5-methylchromone (3), altechromone A (4), norlichexanthone (5), griseoxanthone C (6), 1,3,5,6-tetrahydroxy-8-methylxanthone (7), griseofulvin (8), 6-O-desmethylgriseofulvin (9), dechlorogriseofulvin (10), and 5,6-dihydro-4-methyl-2H-pyran-2-one (11) were identified. The structures of the compounds were elucidated using spectroscopic analyses. The absolute configurations of the chiral centers of sajaroketides A and B were determined using time-dependent density functional theory (TDDFT)-based calculations of the Electronic Circular Dichroism (ECD) spectra. The inhibitory effects of these compounds on urease activity and the growth of Staphylococcus aureus, Escherichia coli, and Candida albicans were observed. Sajaroketide A, altechromone A, and griseofulvin showed significant cardioprotective effects in an in vitro model of S. aureus-induced infectious myocarditis.

Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (1), β-resoantarctines A-C (3, 5, 6) and 8-dehydro-β-resoantarctine A (4), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher’s method, and the biogenetic pathways for compounds 3–6 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 3–6 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds 3, 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.

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) (4S,5R,7S)-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 2R,5R 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

Ten new decalin polyketides, zosteropenilline M (1), 11-epi-8-hydroxyzosteropenilline M (2), zosteropenilline N (3), 8-hydroxyzosteropenilline G (4), zosteropenilline O (5), zosteropenilline P (6), zosteropenilline Q (7), 13-dehydroxypallidopenilline A (8), zosteropenilline R (9) and zosteropenilline S (10), together with known zosteropenillines G (11) and J (12), pallidopenilline A (13) and 1-acetylpallidopenilline A (14), were isolated from the ethyl acetate extract of the fungus Penicillium yezoense KMM 4679 associated with the seagrass Zostera marina. The structures of isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenilline Q (7) and zosteropenilline S (10) were determined using a combination of the modified Mosher’s method and ROESY data. The absolute configurations of zosteropenilline M (1) and zosteropenilline N (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. A biogenetic pathway for compounds 1–14 is proposed. The antimicrobial, cytotoxic and cytoprotective activities of the isolated compounds were also studied. The significant cytoprotective effects of the new zosteropenilline M and zosteropenillines O and R were found in a cobalt chloride (II) mimic in in vitro hypoxia in HEK-293 cells. 1-Acetylpallidopenilline A (14) exhibited high inhibition of human breast cancer MCF-7 cell colony formation with IC₅₀ of 0.66 µM and its anticancer effect was reduced when MCF-7 cells were pretreated with 4-hydroxitamoxifen. Thus, we propose 1-acetylpallidopenilline A as a new xenoestrogen with significant activity against breast cancer.

Background: During the cultivation of the marine fungus KMM 4668 on solid agar medium, the morphological instability of the strain was observed. As a result of the selection work, five intra-strain variants, named KMM 4711, KMM 4712, KMM 4713, KMM 4714, and KMM 4715, were obtained. Methods: The main objectives of this work were to compare the parent strain and its intra-strain variants using multi-locus phylogenetic analysis and to study the UPLC MS metabolite profiles and cytotoxic activities of their extracts. Results: A study of the original strain, KMM 4668, and its intra-strain variants using multi-locus phylogenetic analysis showed that they are sequence identical and belong to Penicillium antarcticum. UPLC MS metabolite profiling of fungal extracts revealed 20 compounds, including cladosporin-related polyketides, carotane sesquiterpenoids, andrastine meroterpenoids, and alkaloids. It was shown that the intra-strain variants KMM 4713 and KMM 4714 differed most strongly from the others in the increased production of cladosporin-related compounds, carotanoids, and the alkaloid chrysogin. In addition, the influence of fungal extracts on the viability of four mammalian cell lines was investigated. Conclusions: It has been shown that the intra-strain variants of P. antarcticum KMM 4668 may be promising sources of bioactive secondary metabolites.

Thirteen new decaline polyketides, namely, zosteropenillines T–W (1–4), 8-hydroxypallidopenilline A (5), 13-epi-zosteropenilline P (6), 11-epi-zosteropenilline N (7), 15-hydroxyzosteropenilline M (8), 8-hydroxyzosteropenilline M (9), 11-epi-zosteropenilline M (10), and zosteropenillines X–Z (11–13), along with 17 known related compounds (14–30) were isolated from the ethyl acetate extract of the marine-derived fungus Penicillium yezoense KMM 4679 cultivated on MgCl₂-containing nutrient medium. The structures of the isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenillines T (1) and V (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. X-ray diffraction analysis data were obtained for the known zosteropenilline S (28). A biogenetic pathway for 1–13 was proposed. The effects of the compounds on Staphylococcus aureus and Candida albicans growth and biofilm formation were observed. Zosteropenillines U (2), Y (12) and Z (13) with higher activity against C. albicans biofilms were nontoxic for normal cardiomyocyte H9c2 cells, making them promising anti-candidal agents. Moreover, zosteropenillines U and Y demonstrated cardioprotective effects in acute ischemia/reperfusion and CoCl₂-mimicking hypoxia in vitro models.