Phosphate ester derivatives of homocamptothecin: synthesis, solution stabilities and antitumor activities

  • Bioorg Med Chem. 2010 May 1;18(9):3140-6. doi: 10.1016/j.bmc.2010.03.039.
Zhenyuan Miao  1 ,  Jing Zhang ,  Liang You ,  Juan Wang ,  Chunquan Sheng ,  Jiangzhong Yao ,  Wannian Zhang ,  Hao Feng ,  Wei Guo ,  Lei Zhou ,  Wenfeng Liu ,  Linjian Zhu ,  Pengfei Cheng ,  Xiaoying Che ,  Wenya Wang ,  Chuan Luo ,  Yulan Xu ,  Guoqiang Dong
Affiliations
  • 1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
PMID: 20371183 DOI: 10.1016/j.bmc.2010.03.039
Abstract

Homocamptothecins (hCPTs) represents a new promising class of Topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three Cancer cell lines and antitumor activity in vivo, and inhibitory properties of Topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0.