Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors.
Basic Information
ID: ALA1781993
Journal: Eur J Med Chem
Title: Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors.
Authors: Liu W, Zhu L, Guo W, Zhuang C, Zhang Y, Sheng C, Cheng P, Yao J, Wang W, Dong G, Wang S, Miao Z, Zhang W.
Abstract: 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.
CiteXplore: 21463912
DOI: 10.1016/j.ejmech.2011.03.024
Patent ID: ┄