Synthesis of 9-(Heteroarylmethylidene)amino Derivatives of Homocamptothecin with Biological Activities

✍ Scribed by Wei Guo; Zhenyuan Miao; Chunquan Sheng; Jianzhong Yao; Wenfeng Liu; Lingjian Zhu; Yongqiang Zhang; Pengfei Cheng; Guoqiang Dong; Chunlin Zhuang; Wannian Zhang

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 430 KB
• Volume: 8
• Category: Article
• ISSN: 1612-1872
• DOI: 10.1002/cbdv.201000271

✦ Synopsis

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 (IC~50~=0.046 μM) and HTC‐116 tumor cells (IC~50~=3.67 μM), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A‐549.