Synthesis of 9‐(Heteroarylmethylidene)amino Derivatives of Homocamptothecin with Biological Activities |
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| Authors: | Wei Guo Zhenyuan Miao Chunquan Sheng Jianzhong Yao Wenfeng Liu Lingjian Zhu Yongqiang Zhang Pengfei Cheng Guoqiang Dong Chunlin Zhuang Wannian Zhang |
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| Institution: | 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: | Six 9‐(heteroarylmethylidene)amino derivatives, 2a – 2f , of homocamptothecin were synthesized for the first time by total synthesis in 22 steps and biologically evaluated as inhibitors of topoisomerase I. Moreover, the antitumor activities of 2a – 2f against three human tumor cell lines, i.e., A‐549, MDA‐MB‐435, and HCT‐116, were determined and the results showed that compound 2c was the most active homocamptothecin derivative against the A‐549 (IC50=0.046 μM ) and HTC‐116 tumor cells (IC50=3.67 μM ), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A‐549. |
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| Keywords: | Homocamptothecin derivatives Topoisomerase I inhibiton Antitumor activity Cytotoxic activity Inhibitors |
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