Abstract
A new series of N-(2-(1H-benzo[d]imidazol-2-yl)phenyl) cinnamides was prepared and evaluated for their in vitro cytotoxic activity using various cancer cell lines viz. A549 (human non-small cell lung cancer), MDA-MB-231 (human triple negative breast cancer), B16-F10 (mouse melanoma), BT-474 (human breast cancer), and 4 T1 (mouse triple negative breast cancer). In the series of tested compounds, 12h showed potent cytotoxic activity against non-small cell lung cancer cell line with IC50 value of 0.29 ± 0.02 µM. The cytoxicity of most potent compound 12h was also tested on NRK-52E (normal rat kidney epithelial cell line) and showed less cytotoxicity compared to cancer cells. Tubulin polymerization assay indicated that the compound 12h was able to impede the cell division by inhibiting tubulin polymerization. Moreover, molecular docking study also suggested the binding of 12h at the colchicine-binding site of the tubulin protein. Cell cycle analysis revealed that the compound 12h arrests G2/M phase. In addition, 12h induced apoptosis in A549 cell lines was evaluated by various staining studies like acridine orange, DAPI, analysis of mitochondrial membrane potential, annexin V-FITC, and DCFDA assays.
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