Discovery of a DNA Topoisomerase I Inhibitor Huanglongmycin N and Its Congeners from Streptomyces sp. CB09001

  • J Org Chem. 2021 Dec 3;86(23):16675-16683. doi: 10.1021/acs.joc.1c01939.
Saibin Zhu  1 ,  Yeji Wang  1 ,  Zhongqing Wen  1 ,  Yanwen Duan  1  2  3 ,  Yong Huang  1  3
Affiliations
  • 1. Xiangya International Academy of Translational Medicine, Central South University, Changsha, Hunan 410013, China.
  • 2. Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, Hunan 410013, China.
  • 3. National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, Hunan 410013, China.
PMID: 34709824 DOI: 10.1021/acs.joc.1c01939
Abstract

Huanglongmycin (HLM) congeners G-N (7-14) were isolated from Streptomyces sp. CB09001. Among them, 10-12 possesses a tricyclic scaffold with benzene-fused pyran/pyrone, confirmed by X-ray single crystal diffraction analysis of 12. The structure-activity relationship study of 1, 13, and 14 revealed not only the stronger cytotoxicity of 14 against tested Cancer cells but also the critical role of the C-7 ethyl group of 14 in its binding to the DNA-topoisomerase I complex.

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