School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, PR China.
Chem Biodivers. 2011 Jul;8(7):1266-73. doi: 10.1002/cbdv.201000271.
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.
首次通过全合成的方法以 22 步反应合成了 6 个 9-（杂芳基亚甲基）氨基衍生物 2a-2f 作为拓扑异构酶 I 的抑制剂，并对其进行了生物评价。此外，还测定了 2a-2f 对三种人肿瘤细胞系 A-549、MDA-MB-435 和 HCT-116 的抗肿瘤活性，结果表明化合物 2c 是对 A-549（IC50=0.046 μM）和 HCT-116 肿瘤细胞最具活性的喜树碱衍生物（IC50=3.67 μM），对肺癌细胞系 A-549 的活性约为参考药物拓扑替康（TPT）的 50 倍。
