Design, synthesis, in vitro anticancer activity, and molecular docking studies of new (R)-carvone-pyrazole-1,2,3-triazoles

Abstract

In the current study, (R)-carvone was utilized as a starting material for the efficient synthesis of several hybrid compounds of the type pyrazole-isoxazole 4a-l and pyrazole-1,2,3-triazole 5a-c using 1,3-dipolar cycloaddition reaction. The target products were obtained in good yields and were characterized by NMR (1H and 13C) and HRMS analysis. The newly synthesized hybrid compounds pyrazole-isoxazole (4a-l) and pyrazole-1,2,3-triazole (5a-c) were evaluated for their cytotoxic activity against four human cancer cells, namely, HT-1080, MCF-7, A549, and MDA-MB-231 using viability testing tetrazolium dye (3-[4,5-dimethyl- thiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT). All the hybrid compounds 4a-d derivatives showed a very low anti-cancer activity (IC50 ≥ 100 μM) against the selected cells. However, the combination of pyrazole and 1,2,3-triazole nucleus caused an average cytotoxic effect with an IC50 value of 18.25 µM against HT-1080 cells. 15 compounds (4a to 4l, and 5a, 5b, and 5c) were docked in the active site of Bcl-2 protein as the most targeted protein in cancer research, and the results were good enough to confirm experimental results supporting that the compound 4d is a potential Bcl-2 inhibitor.