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

School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
Chemistry & Biodiversity (Impact Factor: 1.52). 07/2011; 8(7):1266-73. DOI: 10.1002/cbdv.201000271
Source: PubMed


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.

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