咪唑并[2,1-b]噻唑-苯并咪唑轭合物的合成及作为微管靶向剂的生物评价。
Synthesis and biological evaluation of imidazo[2,1-b]thiazole-benzimidazole conjugates as microtubule-targeting agents.
机构信息
Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India; Academy of Scientific and Innovative Research, New Delhi 110 025, India.
Medicinal Chemistry and Biotechnology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500007, India.
出版信息
Bioorg Chem. 2018 Apr;77:515-526. doi: 10.1016/j.bioorg.2018.02.005. Epub 2018 Feb 12.
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 IC value 1.08 µM. 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 µM. Moreover, the apoptotic inducing properties of compound 6d was confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and annexin V-FITC assay. Further, molecular docking studies revealed that compound 6d occupied the colchicine binding site.
一系列咪唑并[2,1-b]噻唑-苯并咪唑缀合物被合成，并评估了它们对四种人癌细胞系（即 HeLa（宫颈）、A549（肺）、MCF-7（乳腺）和 DU-145（前列腺））以及正常 HEK-293 细胞系的抗增殖活性。其中，缀合物 6d 对人肺癌细胞系 A549 表现出显著的细胞毒性，IC 值为 1.08 µM。此外，细胞周期分析显示，该化合物将细胞周期阻滞在 A549 细胞的 G2/M 期。此外，微管聚合实验结果表明，该缀合物（6d）对微管组装具有显著的抑制作用，IC50 值为 1.68 µM。此外，通过 Hoechst 染色、线粒体膜电位（ΔΨm）和 Annexin V-FITC 测定证实了化合物 6d 的诱导凋亡特性。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。
Zotero 插件