Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents
Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents
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DOI：
10.1016/j.bioorg.2018.02.005
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发表时间：
2018-04-01
影响因子：
5.1
通讯作者：
Kamal, Ahmed
中科院分区：
文献类型：
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作者：
Baig, Mirza Feroz;Nayak, V. Lakshma;Kamal, Ahmed
合成了一系列咪唑并[2,1-b]噻唑-苯并咪唑缀合物，并评估了它们对四种人类癌细胞系的抗增殖活性，即： HeLa（宫颈）、A549（肺）、MCF-7（乳腺癌）和 DU-145（前列腺）以及正常 HEK-293 细胞系。其中，缀合物6d对人肺癌细胞系A549表现出显着的细胞毒性，IC50值为1.08μM。此外，细胞周期分析表明，该化合物将A549细胞的细胞周期阻滞在G2/M期。此外，微管蛋白聚合测定结果表明，该缀合物（6d）对微管蛋白组装表现出显着的抑制作用，IC50值为1.68μM。此外，化合物6d的细胞凋亡诱导特性通过Hoechst染色、线粒体膜电位（Delta Psi m）测量和膜联蛋白V-FITC测定证实。此外，分子对接研究表明化合物 6d 占据了秋水仙碱结合位点。 (C) 2018 Elsevier Inc. 保留所有权利。
A series of imidazo[2,1-b]thiazole-benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines i.e.; HeLa (cervical), A549 (lung), MCF-7 (breast) and DU-145 (prostate) along with normal HEK-293 cell line. Amongst them, conjugate 6d displayed significant cytotoxicity against human lung cancer cell line, A549 with IC50 value 1.08 mu M Further, cell cycle analysis revealed that this compound arrested the cell cycle at G2/M phase in A549 cells. Furthermore, the tubulin polymerization assay results suggest that this conjugate (6d) exhibits significant inhibitory effect on the tubulin assembly with an IC50 value of 1.68 mu M. Moreover, the apoptotic inducing properties of compound 6d was confirmed by Hoechst staining, measurement of mitochondrial membrane potential (Delta Psi m)and annexin V-FITC assay. Further, molecular docking studies revealed that compound 6d occupied the colchicine binding site. (C) 2018 Elsevier Inc. All rights reserved.