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Synthesis and Biological Evaluation of 7‐Alkenyl Homocamptothecins as Potent Topoisomerase I Inhibitors |
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| Authors: | Ning Lei Wenfeng Liu Zhenyuan Miao Chunlin Zhuang Chunquan Sheng Wei Guo Guoqiang Dong Jianzhong Yao Pengfei Cheng Wannian Zhang |
| Affiliation: | 1. Department of Quality Assurance, Lian Yun Gang JARI Pharmaceutical Co., Ltd., 18 Zhenhua Road, Lianyungang 222100, P.?R. China;2. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.?R. China (W. Z.: phone/fax: +86‐21‐81871243;3. Z. M.: phone: +86‐21‐81871233) |
| 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. |
| Keywords: | Homocamptothecin Camptothecin Topoisomerase I Antitumor activity Inhibitors |