Synthesis and biological evaluation of new homocamptothecin analogs

Yu Luo; Shanbao Yu; Linjiang Tong; Qingqing Huang; Wei Lu; Yi Chen

doi:10.1016/j.ejmech.2012.05.002

Synthesis and biological evaluation of new homocamptothecin analogs

Eur J Med Chem. 2012 Aug:54:281-6. doi: 10.1016/j.ejmech.2012.05.002. Epub 2012 May 15.

Authors

Yu Luo¹, Shanbao Yu, Linjiang Tong, Qingqing Huang, Wei Lu, Yi Chen

Affiliation

¹ Institute of Drug Discovery and Development, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, 3663 North Zhongshan Road, East China Normal University, Shanghai 200062, China.

PMID: 22647222
DOI: 10.1016/j.ejmech.2012.05.002

Abstract

In order to increase the stability of E-ring of homocamptothecins, the electron-withdrawing group -OH or -OAc was induced to α position of ring-E lactone. Ten new homocamptothecin analogs were synthesized. Most compounds showed potent in vitro anticancer activity and potent Topo I inhibition, which was equal or superior to that of CPT, SN-38 and 10-HCPT. The stability studies of this series also displayed significant improvement of the stability.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Camptothecin / analogs & derivatives*
Camptothecin / chemical synthesis
Camptothecin / chemistry
Camptothecin / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Chemistry Techniques, Synthetic
DNA Topoisomerases, Type I / metabolism
Drug Stability
Humans
Structure-Activity Relationship
Topoisomerase I Inhibitors / chemical synthesis*
Topoisomerase I Inhibitors / chemistry
Topoisomerase I Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Topoisomerase I Inhibitors
homocamptothecin
DNA Topoisomerases, Type I
Camptothecin