Synthesis and Biological Evaluation of 7-Alkenyl Homocamptothecins as Potent Topoisomerase I Inhibitors

Abstract Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven‐membered β ‐hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7‐alkenyl‐homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A‐549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I‐inhibition activity.