Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500607, India.
ChemMedChem. 2012 Feb 6;7(2):292-300. doi: 10.1002/cmdc.201100511. Epub 2012 Jan 12.
A new series of 3-substituted 2-phenylimidazo[2,1-b]benzothiazoles (3 a-h) were synthesized by C-arylation of 2-arylimidazo[2,1-b]benzothiazoles using palladium acetate as catalyst, and the resulting compounds were evaluated for their anticancer activity. Compounds 3 a, 3 e, and 3 h exhibited good antiproliferative activity, with GI50 values in the range of 0.19-83.1 μM. Compound 3 h showed potent anticancer efficacy against 60 human cancer cell lines, with a mean GI50 value of 0.88 μM. This compound also induced cell-cycle arrest in the G2/M phase and inhibited tubulin polymerization followed by activation of caspase-3 and apoptosis. A high-throughput tubulin polymerization assay showed that the level of inhibition for compound 3 h is similar to that of combretastatin A-4. Molecular modeling studies provided a molecular basis for the favorable binding of compounds 3 a, 3 e, and 3 h to the colchicine binding pocket of tubulin.
新的一系列 3-取代的 2-苯基咪唑并[2,1-b]苯并噻唑（3a-h）通过使用醋酸钯作为催化剂的 2-芳基咪唑并[2,1-b]苯并噻唑的 C-芳基化反应合成，并且评价所得化合物的抗癌活性。化合物 3a、3e 和 3h 表现出良好的增殖抑制活性，GI50 值在 0.19-83.1 μM 的范围内。化合物 3h 对 60 个人类癌细胞系表现出有效的抗癌功效，平均 GI50 值为 0.88 μM。该化合物还诱导细胞周期停滞在 G2/M 期，并抑制微管蛋白聚合，随后激活 caspase-3 和细胞凋亡。高通量微管蛋白聚合测定表明，化合物 3h 的抑制水平与 combretastatin A-4 相似。分子建模研究为化合物 3a、3e 和 3h 与微管蛋白的秋水仙碱结合口袋的良好结合提供了分子基础。
