Design, Total Synthesis And Antitumor Activity Of 10-Substituted Homocamptothecin Derivatives As Topoisomerase I Inhibitors

Camptothecin and its derivates as the most important Topoisomerase I inhibitors had been good activity against several tumor cells in vitro and in vivo. Recently three camptothecin derivates had been approved for cancer therapy. Homocamptothecin, a novel CPT analogue which contains an expanded seven-memberedβ-hydroxylactone replacing six-memberedα-hydroxylactone, had shown elevated antitumor activity and improved stability without species difference.Granted by the National Natural Science Foundation of China(No.30371689) and Shanghai Major Program Science and Technology Foundation(No. 064319009),we had designed and synthesized two kinds of twenty-two novel homocamptothecins base on a new total synthetic method designed by our group. Antitumor activities were evaluated by standard MTT method and the result showed that eleven compounds had potent activity against tumor cells in vitro.