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.
Yu Luo  1 ,  Shanbao Yu ,  Linjiang Tong ,  Qingqing Huang ,  Wei Lu ,  Yi Chen
Affiliations
  • 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.