A series of novel 7-acyl derivatives of homocamptothecin (hCPT) were designed and synthesized with the purpose to improve antitumor activity of hCPT, via Minisci free-radical reaction from 10-methoxyhomocamptothecin. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, MDA-MB-435 and HCT116). For MDA-MB-435 cell line, compounds, 6a, 6b, 6k and all of 7-alkylcabonyl homocamptothecin derivatives showed higher in vitro inhibitory activities than topotecan (TPT). Furthermore, compounds 6d, 6e, and 6k showed highly potent inhibitory activities with the IC50 values from less than 1 nM to 2.2 nM. In Topoisomerase I (Topo I)-induced DNA cleavage assay, compounds 6a, 6d, and 6k, as compared to CPT, revealed higher Topo I inhibitory activity.
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