Romagnoli Romeo, Baraldi Pier Giovanni, Carrion Maria Dora, Lopez Cara Carlota, Preti Delia, Fruttarolo Francesca, Pavani Maria Giovanna, Tabrizi Mojgan Aghazadeh, Tolomeo Manlio, Grimaudo Stefania, Di Cristina Antonella, Balzarini Jan, Hadfield John A, Brancale Andrea, Hamel Ernest
Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
J Med Chem. 2007 May 3;50(9):2273-7. doi: 10.1021/jm070050f. Epub 2007 Apr 10.
Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. Although many more 3-amino derivatives have been synthesized so far, the most promising compound in this series was 2-amino-6-methyl-3-(3,4,5-trimethoxybenzoyl)benzo[b]thiophene, which inhibits cancer cell growth at subnanomolar concentrations and interacts strongly with tubulin by binding to the colchicine site.
基于2-氨基-3-(3,4,5-三甲氧基苯甲酰基)苯并[b]噻吩分子骨架及其3-氨基位置异构体，合成了两个新系列的微管蛋白聚合抑制剂，并对其抗增殖活性、微管蛋白聚合抑制作用和细胞周期效应进行了评估。尽管到目前为止已经合成了更多的3-氨基衍生物，但该系列中最有前景的化合物是2-氨基-6-甲基-3-(3,4,5-三甲氧基苯甲酰基)苯并[b]噻吩，它在亚纳摩尔浓度下就能抑制癌细胞生长，并通过与秋水仙碱位点结合而与微管蛋白强烈相互作用。
