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

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 ( 1 H and 13 C) 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 (IC 50 > 100 mu M) against the selected cells. However, the combination of pyrazole and 1,2,3-triazole nucleus caused an average cytotoxic effect with an IC 50 value of 18.25 mu M against HT-1080 cells. 15 compounds ( 4a to 4l , and 5a, 5b , and 5c ) were docked in the active site of Bcl2 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.(c) 2022 Elsevier B.V. All rights reserved.