Efficient Four-Component Synthesis of 1,2,4-Triazolo[1,5-α]pyrimidines and Their In Vitro Antiproliferative Studies

Triazolopyrimidines are emerging as potential anticancer agents. Herein, we report a novel one-pot four component synthesis of 2-((2-oxo-2-phenylethyl/benzyl)thio)-10-phenyl-4,10-dihydro-9H-indeno[1,2-d][1,2,4]-Triazolo[1,5-alpha]pyrimidin-9-ones by the reaction of 1,3-indanedione, aromatic aldehyde, 5-amino-4H-1,2,4-Triazol-3-thiol and phenacyl bromide in acetic acid with piperidine as catalyst at 90 degrees C for 13 hours. All the final compounds were identified on the basis of their FT-IR, H-1 NMR, (CNMR)-C-13 and HRMS. The synthesized compounds were evaluated for their cell growth inhibition potential using MTT and wound healing assay, (13)compounds induced concentration dependent inhibition with IC50 below 10 mu M against breast cancer cell lines (MCF-7). Further, the molecular docking simulation were carried out for all the derivatives, amongst these thio phenacyl, 2,4-dichlorophenyl 9H-indeno [1,2,4]-Triazolo[1,5-alpha]pyrimidin-9-one (5 g) shows good binding interaction with amino acid residues. This is further confirmed by wound healing assay which shows that 5 g inhibits cell migration at increasing concentrations.