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

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.

Some diphosphates and triphosphates homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and the solution stability both at pH 7.4 and at pH 3.0.Figure optionsDownload as PowerPoint slide