Herbimycins D鈥揊, Ansamycin Analogues from Streptomyces sp. RM-7-15

详细信息    查看全文

• 作者：Khaled A. Shaaban ; Xiachang Wang ; Sherif I. Elshahawi ; Larissa V. Ponomareva ; Manjula Sunkara ; Gregory C. Copley ; James C. Hower ; Andrew J. Morris ; Madan K. Kharel ; Jon S. Thorson
• 刊名：Journal of Natural Products
• 出版年：2013
• 出版时间：September 27, 2013
• 年：2013
• 卷：76
• 期：9
• 页码：1619-1626
• 全文大小：380K
• 年卷期：v.76,no.9(September 27, 2013)
• ISSN：1520-6025

文摘

Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian Mountains of eastern Kentucky). High-resolution electrospray ionization mass spectrometry and ultraviolet absorption profiles of metabolites from one of the isolates (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D鈥揊 (1鈥?b>3). In addition, herbimycin A (4), dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15. Herbimycins A and D鈥揊 (1鈥?b>3) displayed comparable binding affinities to the Hsp90伪. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of nontoxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease.