Griseofulvin enantiomers and bromine-containing griseofulvin derivatives with antifungal activity produced by the mangrove endophytic fungus Nigrospora sp.QQYB1  

作　　者：Ge Zou Wencong Yang Tao Chen Zhaoming Liu Yan Chen Taobo Li Gulab Said Bing Sun Bo Wang Zhigang She 

机构地区：[1]School of Chemistry,Sun Yat-sen University,Guangzhou 510275,China [2]State Key Laboratory of Applied Microbiology Southern China,Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application,Institute of Microbiology,Guangdong Academy of Sciences,Guangzhou 510070,China [3]School of Pharmacy,Anhui Medical University,Hefei 230032,China [4]Department of Chemistry,Women University Swabi,Swabi 23430,Pakistan

出　　处：《Marine Life Science & Technology》2024年第1期102-114,共13页海洋生命科学与技术（英文）

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).

摘　　要：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.

关 键 词：Mangrove endophytic fungus Nigrospora sp. GRISEOFULVIN Antifungal activity 

分 类 号：Q178.53[生物学—水生生物学]