SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL 1, 2, 3-TRIAZOLE-CHALCONE HYBRIDS AS ANTI-PROLIFERATIVE AGENTS AGAINST HT29 COLON CANCER CELLSAbstract
Independent studies have shown that chalcones and 123 triazole exhibited cytotoxic effects on human cancer cell lines. In the present study, we prepared a series of novel 1,2,3-triazole-chalcone hybrid compounds and evaluated the cytotoxic effect and probable mode of action in HT29 colon cancer cell line. Among the 10 evaluated compounds, compounds 4 (3-nitro) and 8 (3-chloro) were the only compounds that elicited a dose-dependent decrease in cell viability (IC50 values 9.7 and 33 M, respectively) of HT 29 cells. The same compounds exhibited a significant inhibitory effect on the cell proliferation and colony-forming capability of HT29 cells. Co-administration of compounds 4 and 8 with electron transport chain inhibitors and mitochondrial K+-ATP channel blockers in H9C2 enhanced the anti-proliferative capacity of the compound. Furthermore, Insilco molecular docking studies revealed that the anti-proliferative effect of these compounds could be attributed to interactions with the colchicine-binding site of tubulin. In conclusion, our results demonstrated that novel 1,2,3-triazole-chalcone hybrid can be a potent therapeutic agent against HT-29 cells, and its anti proliferating capacity against the cancer cell can be augmented in the presence of mitochondrial complex-I or mitochondrial KATP channel inhibitor.