Diacetoxy iodobenzene mediated regioselective synthesis and characterization of novel [1,2,4]triazolo[4,3-a]pyrimidines: apoptosis inducer, antiproliferative activities and molecular docking studies.

Prompt and regioselective synthesis of eleven novel [1,2,4]triazolo[4,3-a]pyrimidines , intramolecular oxidative-cyclization of 2-(2-arylidenehydrazinyl)-4-methyl-6-phenylpyrimidine derivatives has been demonstrated here using diacetoxy iodobenzene (DIB) as inexpensive and ecofriendly hypervalent iodine(III) reagent in CHCl at room temperature. Regiochemistry of final product has been established by developing single crystal and studied X-ray crystallographic data for two derivatives and without any ambiguity. These prominent [1,2,4]triazolo[4,3-a]pyrimidines were evaluated for human osteosarcoma bone cancer (MG-63) and breast cancer (MCF-7) cell lines using MTT assay to find potent antiproliferative agent and also on testicular germ cells to find potent apoptotic inducing activities. All compounds show significant cytotoxicity, particularly 3-(2,4-dichlorophenyl)-5-methyl-7-phenyl-[1,2,4]triazolo[4,3-a]pyrimidine () was found significant apoptotic inducing molecule, as well as the most potent cytotoxic agent against bone cancer (MG-63) and breast cancer (MCF-7) cell lines with GI value 148.96 µM and 114.3 µM respectively. Molecular docking studies has been carried out to see the molecular interactions of synthesized compounds with the protein thymidylate synthase (PBD ID: 2G8D).Communicated by Ramaswamy H. Sarma.