5-氨基-2-芳酰基喹啉类化合物作为高活性的微管蛋白聚合抑制剂。

5-Amino-2-aroylquinolines as highly potent tubulin polymerization inhibitors.

机构信息

College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, Republic of China.

出版信息

J Med Chem. 2010 Mar 11;53(5):2309-13. doi: 10.1021/jm900685y.

PMID:20148562

Abstract

A series of aroylquinoline derivatives were synthesized and evaluated for anticancer activity. 5-Amino-6-methoxy-2-aroylquinoline 15 showed more potent antiproliferative activity (IC(50) values ranging from 0.2 to 0.4 nM) as compared to 1a (combretastatin A-4) (IC(50) = 1.9-835 nM) against various human cancer cell lines and a MDR-resistant cancer cell line. Compound 15 (IC(50) = 1.6 microM) exhibited more potent inhibition of tubulin polymerization than 1a (IC(50) = 2.1 microM) and showed strong binding property to the colchicine binding site of microtubules.

摘要

合成了一系列芳酰基喹啉衍生物，并对其进行了抗癌活性评价。与 1a（康普瑞汀 A-4）（IC₅₀=1.9-835 nM）相比，5-氨基-6-甲氧基-2-芳酰基喹啉 15 对多种人癌细胞系和多药耐药癌细胞系表现出更强的增殖抑制活性（IC₅₀值范围为 0.2-0.4 nM）。化合物 15（IC₅₀=1.6 μM）对微管蛋白聚合的抑制作用强于 1a（IC₅₀=2.1 μM），并表现出与秋水仙碱结合微管位点的强结合特性。