A Click Synthesis, Molecular Docking, Cytotoxicity on Breast Cancer (MDA-MB 231) and Anti-HIV Activities of New 1,4-Disubstituted-1,2,3-Triazole Thymine Derivatives

Abstract

A new series of 1,4-disubstituted-1,2,3-triazolethymine derivatives (VIa–e) were synthesized and characterized by spectroscopic studies. The in vitro cytotoxic activities of selected compounds against human cancer cell line (MDA-MB 231) were evaluated by MTT assay. 4-Azido-N-substituted-benzenesulfonamides (Vc–e) and 4,4'-(4,4'-((5-methyl-2,4-dioxopyrimidine-1,3(2H,4H)-diyl)bis(methylene))-bis(1H-1,2,3-triazole-4,1-diyl))-bis(N-(4-methyl pyrimidin-2-yl)benzenesulfonamide) (VIc) displayed a significant cytotoxic activity with IC50 values of 1.61, 1.41, 1.61 and 1.81 μM, respectively. Molecular docking study of 4‑azido-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (Vd) and 4,4'-(4,4'-((5-methyl-2,4-dioxopyrimidine-1,3(2H,4H)-diyl)bis(methylene))-bis(1H-1,2,3-triazole-4,1-diyl))-bis (N-(4-methyl pyrimidin-2-yl)benzenesulfonamide) (VIc) showed hydrogen bonding with the amino acid residues of the receptors 1X7R and 1A53, respectively. These derivatives are useful as starting points for further study of new anticancer drugs and to confirm the potential of triazole-sulfonamide analogues as lead compounds in anticancer drug discovery. In addition, 1,4-disubstituted-1,2,3-triazolethymine derivatives (VIa–e) were evaluated in vitro for antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells. The results showed that 1,4-disubstituted-1,2,3-triazolethymine derivatives (VIc–e) possess a potent activity against HIV-1 replication with IC50 values of 11.42, ≥15.25,and 14.36 μM, SI > 4, ≤6, >9, respectively.