Efficient synthesis of new tetrazole-based sulfonamide derivatives: cytotoxicity and molecular docking studies on HT29 cancer cell line
Subject Areas : Iranian Journal of Organic Chemistry
Keywords: Tetrazole, Sulfonamides, [2+3] Cycloaddition, Cytotoxicity, colorectal cancer, HT29 cancer cell line, Molecular docking studies,
Abstract :
In this study, two novel tetrazole-based sulfonamide derivatives, N-((2H-tetrazol-5-yl)methyl)(phenyl)-Ntosylmethanamine (5a) and N-((2H-tetrazol-5-yl)methyl)-N-tosylpyridin-2-amine (5b) were synthesized through an azide-nitrile cycloaddition reaction. The reaction proceeded smoothly in good yields (70-78%) using ZnBr2 as a robust catalyst and H2O/2-propanol as a green solvent system. The structure of the products was confirmed by FT-IR, 1HNMR, 13CNMR, and LC-Mass analysis. Cytotoxicity evaluations of 5a and 5b on HT29 cell line demonstrated that compound 5b has the most potent in vitro antiproliferative activity with IC50 values of 24.66 ± 4.51 μM. Although, compound 5a showed anti-proliferative activity with IC50 values of 85.57 ± 6.61 μM on HT29 cells, comparable to Cisplatin, as a potent known anticancer drug with IC50 values of 7.49 ± 1.71 μM. Furthermore, we performed molecular docking studies to investigate the possible drug-likeness of the synthesized molecules 5a and 5b, from which the results suggested that compound 5b could be a promising candidate for p53 inhibition.