Zhou Yan-Hui, Zhang Ming, Zhu Rong-Xiu, Zhang Jiao-Zhen, Xie Fei, Li Xiao-Bin, Chang Wen-Qiang, Wang Xiao-Ning, Zhao Zun-Tian, Lou Hong-Xiang
Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University , 44 Wenhua West Road, Jinan 250012, People's Republic of China.
School of Chemistry and Chemical Engineering, Shandong University , 27 Shanda Nanlu, Jinan 250100, People's Republic of China.
J Nat Prod. 2016 Sep 23;79(9):2149-57. doi: 10.1021/acs.jnatprod.5b00998. Epub 2016 Aug 24.
Twelve new heptaketides, biatriosporins A-L (1-12), biatriosporin M (13) (a ramulosin derivative), and 19 known compounds (14-32) were isolated from the endolichenic fungus Biatriospora sp. (8331C). The structures of these compounds were determined by analyzing MS and NMR data. The absolute configurations of compounds 1, 2, 7, and 9 were determined by single-crystal X-ray diffraction analysis, whereas compound 10 was deduced with Mosher's method. Four of the compounds were active in an antifungal assay. The most potent compound, compound 4, also sensitized clinically derived azole-resistant Candida albicans strains to fluconazole (FLC). A mechanistic investigation revealed that 4 inhibited the function of efflux pumps and reduced the transcriptional expression of the efflux-pump-related genes CDR1 and CDR2.
从内生地衣真菌Biatriospora sp. (8331C)中分离出12种新的七肽，即双孢菌素A-L（1-12）、双孢菌素M（13）（一种ramulosin衍生物）以及19种已知化合物（14-32）。通过分析质谱和核磁共振数据确定了这些化合物的结构。化合物1、2、7和9的绝对构型通过单晶X射线衍射分析确定，而化合物10则用Mosher方法推导得出。其中四种化合物在抗真菌试验中具有活性。最有效的化合物，即化合物4，还使临床分离的耐唑类白色念珠菌菌株对氟康唑（FLC）敏感。机理研究表明，4抑制了外排泵的功能，并降低了外排泵相关基因CDR1和CDR2的转录表达。
