Topoisomerase I‐Mediated Antiproliferative Activity of 10‐Substituted and 12‐Substituted Homocamptothecins |
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| Authors: | Wei Guo Wenfeng Liu Lingjian Zhu Yongqiang Zhang Pengfei Cheng Guoqiang Dong Chunlin Zhuang Jianzhong Yao Chunquan Sheng Zhenyuan Miao Wannian Zhang |
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| Affiliation: | 1. School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P.?R. China, (W. Zhang, phone/fax: 86‐21‐81871243;2. , Z. Miao, phone/fax: 86‐21‐81871233;3. , C. Sheng, phone/fax: 86‐21‐81871233) |
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| Abstract: | ![]()
Homocamptothecin (hCPT) is an E‐ring modified camptothecin (CPT) analogue, which showed pronounced inhibitory activity of topoisomerase I. In search of novel hCPT‐type anticancer agents, two series of hCPT derivatives were synthesized and evaluated in vitro against three human tumor cell lines. The results indicated that the 10‐substituted hCPT derivatives had a considerably higher cytotoxic activity than the 12‐substituted ones. Among the 10‐substituted compounds, 8a, 8b, 9b , and 9i showed an equivalent or even more potent activity than the positive control drug topotecan against the lung cancer cell line A‐549. Moreover, the hCPT analogues 8a and 8b exhibited a higher topoisomerase I inhibitory activity than CPT at a concentration of 100 μM . |
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| Keywords: | Homocamptothecin derivatives Topoisomerase I inhibiton Antitumor activity Cytotoxic activity Topotecan Structure?activity relationship (SAR) Inhibitors |
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