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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 IC 50 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.

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., (© 2024. The Author(s).)

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.

The KMM 4639 strain was identified as Amphichorda sp. based on two molecular genetic markers: ITS and β-tubulin regions. Chemical investigation of co-culture marine-derived fungi Amphichorda sp. KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of five new quinazolinone alkaloids felicarnezolines A-E ( 1 - 5 ), a new highly oxygenated chromene derivative oxirapentyn M ( 6 ) and five previously reported related compounds. Their structures were established using spectroscopic methods and by comparison with related known compounds. The isolated compounds showed low cytotoxicity against human prostate and breast cancer cells but felicarnezoline B ( 2 ) protected rat cardiomyocytes H9c2 and human neuroblastoma SH-SY5Y cells against CoCl 2 -induced damage.

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.

Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide ( 1 ) from the marine-derived fungus Penicillium dimorphosporum KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound 1 is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound 1 resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes.

Chemical investigation of a coculture of the marine-derived fungi Beauveria felina KMM 4639 and Aspergillus carneus KMM 4638 led to the identification of three new drimane-type sesquiterpenes, asperflavinoids B, D and E ( 2 , 4 , 5 ), and nine previously reported related compounds. The structures of these compounds were established using spectroscopic methods and by comparison with known analogues. We also investigated the cytotoxic activity of the isolated compounds against several cancer and normal cell lines. Asperflavinoid C ( 3 ) and ustusolate E ( 9 ) exerted a significant effect on human breast cancer MCF-7 cell viability, with IC 50 values of 10 µM, and induced in caspase-dependent apoptosis and arrest of the MCF-7 cell cycle in the G2/M phase in these cells.