Abstract
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•A series of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates were synthesised and evaluated for antiproliferative activity.•Conjugates 5d and 5u exhibited promising cytotoxicity.•The tested conjugates 5d and 5u induced cell-cycle arrest in the G2/M phase and inhibited tubulin polymerization.•Reactive oxygen species (ROS) detection and annexin V–FITC/PI assays indicated that 5d and 5u induces apoptosis.
A series of benzo[d]imidazo[2,1-b]thiazole-chalcone conjugates (5a-aa) were designed, synthesized and evaluated for their cytotoxic potency against a panel of human cancer cell lines like lung (A-549), breast (MDA MB-231), prostrate (DU-145) and colon cancer (HT-29). Preliminary results revealed that some of these conjugates like 5d and 5u exhibited significant antiproliferative effect against human breast cancer (MDA MB-231) with IC50 values of 1.3 and 1.2 µM respectively. To investigate the mechanistic aspects underlying the activity, the detailed biological studies of these promising conjugates (5d and 5u) were carried out on the MDA MB-231 cancer cells. Flow cytometric analysis revealed that these conjugates induce cell-cycle arrest in the G2/M phase. The tubulin polymerization assay suggests that these conjugates effectively inhibit microtubule assembly. In addition, morphological changes, reactive oxygen species (ROS) detection by 2′, 7′–dichlorofluorescin diacetate (DCFDA) and annexin V–FITC/PI assays indicate that 5d and 5u induces apoptosis. Furthermore, in silico computational studies, including molecular docking studies have been carried out to rationalise the binding modes of these conjugates with the tubulin protein.