(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01....(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.展开更多
Co-culturing the mangrove endophytic fungus Penicillium sclerotiorum THSH-4 with Penicillium sclerotiorum ZJHJJ-18 in PDB medium resulted in the production of nine new azaphilones derivatives,peniazaphilones A—I(1-9)...Co-culturing the mangrove endophytic fungus Penicillium sclerotiorum THSH-4 with Penicillium sclerotiorum ZJHJJ-18 in PDB medium resulted in the production of nine new azaphilones derivatives,peniazaphilones A—I(1-9),and six known azaphilones derivatives(10-15).Their structures were elucidated by analysis of detailed spectroscopic data,single-crystal X-ray diffraction,ECD spectra,^(13)C NMR calculation and DP4+analysis.It is noteworthy that compound 1 with an isoquinoline quinone moiety,was isolated from natural source for the first time.Besides,compound 2 is the third reported phenylhydrazone derivative from fungi.In the bioactivity assays,compounds 1,12,14 and 15(IC_(50)=4.71-17.64μmol/L)exhibited potent inhibition of LPS-induced NO release from RAW264.7 without obvious cytotoxicity within 50μmol/L compared to the positive control indomethacin(IC_(50)=35.27μmol/L).Moreover,compounds 1 and 13 displayed moderate to strong cytotoxicity to A549 and MDA-MB-435,with IC_(50) values in the range of 6.84-14.63μmol/L.Together compound 1 showed moderate broad-spectrum antibacterial activity.展开更多
Marine microorganisms have long been recognized as potential sources for drug discovery.Griseofulvin was one of the first antifungal natural products and has been used as an antifungal agent for decades.In this study,...Marine microorganisms have long been recognized as potential sources for drug discovery.Griseofulvin was one of the first antifungal natural products and has been used as an antifungal agent for decades.In this study,12 new griseofulvin derivatives[(±)-1-2,(+)-3,(±)-4,10-12,and 14-15]and two new griseofulvin natural products(9 and 16)together with six known analogues[(-)-3,5-8,and 13]were isolated from the mangrove-derived fungus Nigrospora sp.QQYB1 treated with 0.3%NaCl or 2%NaBr in rice solid medium.Their 2D structures and absolute configurations were established by extensive spectroscopic analysis(1D and 2D NMR,HRESIMS),ECD spectra,computational calculation,DP4+analysis,and X-ray single-crystal diffraction.Compounds 1-4 represent the first griseofulvin enantiomers with four absolute configurations(2S,6'S;2R,6'R;2S,6'R;2R,6'S),and compounds 9-12 represent the first successful production of brominated griseofulvin derivatives from fungi via the addition of NaBr to the culture medium.In the antifungal assays,compounds 6 and 9 demonstrated significant inhibitory activities against the fungi Colletotrichum truncatum,Microsporum gypseum,and Trichophyton mentagrophyte with inhibition zones varying between 28 and 41 mm(10μg/disc).The structure-activity relationship(SAR)was analyzed,which showed that substituents at C-6,C-7,C-6'and the positions of the carbonyl and double bond of griseofulvin derivatives significantly affected the antifungal activity.展开更多
基金National Natural Science Foundation of China(Nos.U20A2001,81973195,21877133)the Guangdong Marine Economy Development Special Project(Nos.GDNRC[2022]35,GDNRC[2023]39)。
文摘(±)-Mycosphatide A(1a/1b),a pair of highly oxidized enantiomeric polyketides featuring a unique5/5/6/5-fused tetracyclic ring system,were isolated from the mangrove endophytic fungus Mycosphaerella sp.SYSU-DZG01.Their structures were established by extensive spectroscopic analyses,single crystal Xray diffraction,and experimental electronic circular dichroism(ECD)spectra comparison.The plausible biosynthetic pathway of 1 was proposed,which involved the generation of a key spiro[4.5]decane scaffold.Compounds(+)-1a and(-)-1b exhibited significant lipid-lowering activity in 3T3-L1 adipocytes model,with EC50values of 7.85±1.56 and 8.87±0.80μmol/L,respectively.
基金This research was funded by the National Natural Science Foundation of China(Nos.U20A2001,21877133)the National Key R&D Program of China(No.2019YFC0312501)+3 种基金the Key-Area Research and Development Program of Guangdong Province(No.2020B1111030005)the Key Project of Natural Science Foundation of Guangdong Province(No.2016A030311026)the Fundamental Research Funds for the Central Universities(No.20ykjc04)We acknowledge the IARC,SYSU for support towards IR and LC-MS equipment.We also thank SCSIO for generous support towards ECD equipment and X-ray single crystal diffractometer.
文摘Co-culturing the mangrove endophytic fungus Penicillium sclerotiorum THSH-4 with Penicillium sclerotiorum ZJHJJ-18 in PDB medium resulted in the production of nine new azaphilones derivatives,peniazaphilones A—I(1-9),and six known azaphilones derivatives(10-15).Their structures were elucidated by analysis of detailed spectroscopic data,single-crystal X-ray diffraction,ECD spectra,^(13)C NMR calculation and DP4+analysis.It is noteworthy that compound 1 with an isoquinoline quinone moiety,was isolated from natural source for the first time.Besides,compound 2 is the third reported phenylhydrazone derivative from fungi.In the bioactivity assays,compounds 1,12,14 and 15(IC_(50)=4.71-17.64μmol/L)exhibited potent inhibition of LPS-induced NO release from RAW264.7 without obvious cytotoxicity within 50μmol/L compared to the positive control indomethacin(IC_(50)=35.27μmol/L).Moreover,compounds 1 and 13 displayed moderate to strong cytotoxicity to A549 and MDA-MB-435,with IC_(50) values in the range of 6.84-14.63μmol/L.Together compound 1 showed moderate broad-spectrum antibacterial activity.
基金funded by the Guangdong Marine Economy Development Special Project(GDNRC[2022]35,GDNRC[2023]39)the National Natural Science Foundation of China(U20A2001,42276114).
文摘Marine microorganisms have long been recognized as potential sources for drug discovery.Griseofulvin was one of the first antifungal natural products and has been used as an antifungal agent for decades.In this study,12 new griseofulvin derivatives[(±)-1-2,(+)-3,(±)-4,10-12,and 14-15]and two new griseofulvin natural products(9 and 16)together with six known analogues[(-)-3,5-8,and 13]were isolated from the mangrove-derived fungus Nigrospora sp.QQYB1 treated with 0.3%NaCl or 2%NaBr in rice solid medium.Their 2D structures and absolute configurations were established by extensive spectroscopic analysis(1D and 2D NMR,HRESIMS),ECD spectra,computational calculation,DP4+analysis,and X-ray single-crystal diffraction.Compounds 1-4 represent the first griseofulvin enantiomers with four absolute configurations(2S,6'S;2R,6'R;2S,6'R;2R,6'S),and compounds 9-12 represent the first successful production of brominated griseofulvin derivatives from fungi via the addition of NaBr to the culture medium.In the antifungal assays,compounds 6 and 9 demonstrated significant inhibitory activities against the fungi Colletotrichum truncatum,Microsporum gypseum,and Trichophyton mentagrophyte with inhibition zones varying between 28 and 41 mm(10μg/disc).The structure-activity relationship(SAR)was analyzed,which showed that substituents at C-6,C-7,C-6'and the positions of the carbonyl and double bond of griseofulvin derivatives significantly affected the antifungal activity.
