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

Saibin Zhu; Yeji Wang; Zhongqing Wen; Yanwen Duan; Yong Huang

doi:10.1021/acs.joc.1c01939

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. Epub 2021 Oct 28.

Authors

Saibin Zhu¹, Yeji Wang¹, Zhongqing Wen¹, 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Crystallography, X-Ray
Pyrones
Streptomyces*
Structure-Activity Relationship
Topoisomerase I Inhibitors* / pharmacology

Substances

Pyrones
Topoisomerase I Inhibitors