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

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 mu m) and HTC-116 tumor cells (IC50 = 3.67 mu m), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A-549.