Design and synthesis of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone conjugates: study on their apoptosis inducing ability and tubulin polymerization inhibition.

A library of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone derivatives were designed, synthesized and screened for their in vitro cytotoxic activity against BT-474, HeLa, MCF-7, NCI-H460 and HaCaT cells by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized analogues, compound 10ec displayed the highest cytotoxicity with the IC50 value of 0.99 ± 0.01 µM towards BT-474 cancer cell line. The target compound (10ec) was also evaluated for its tubulin polymerization inhibition study. Detailed biological studies such as acridine orange/ethidium bromide (AO/EB), DAPI and annexin V-FITC/propidium iodide staining assay suggested that compound 10ec induced the apoptosis of BT-474 cells. The clonogenic assay revealed that the inhibition of colony formation in BT-474 cells by 10ec in concentration-dependent manner. Moreover, the flow cytometric analysis revealed that 10ec induced apoptosis via cell cycle arrest at the sub-G1 and G2/M phase. In silico studies of sulfonyl piperazine-integrated triazole conjugates unveil that they possess drug-like properties. According to the molecular modelling studies, compound 10ec binds to the colchicine binding site of the tubulin.

New imidazo[2,1-b]thiazole-based aryl hydrazones: unravelling their synthesis and antiproliferative and apoptosis-inducing potential.

Herein, we have designed and synthesized new imidazo[2,1-b]thiazole-based aryl hydrazones (9a-w) and evaluated their anti-proliferative potential against a panel of human cancer cell lines. Among the synthesized compounds, 9i and 9m elicited promising cytotoxicity against the breast cancer cell line MDA-MB-231 with IC50 values of 1.65 and 1.12 µM, respectively. Cell cycle analysis revealed that 9i and 9m significantly arrest MDA-MB-231 cells in the G0/G1 phase. In addition, detailed biological studies such as annexin V-FITC/propidium iodide, DCFH-DA, JC-1 and DAPI staining assays revealed that 9i and 9m triggered apoptosis in MDA-MB-213 cells. Overall, the current work demonstrated the cytotoxicity and apoptosis-inducing potential of 9i and 9m in breast cancer cells and suggested that they could be explored as promising antiproliferative leads in the future.