Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents

Abstract

A series of hybrid aza heterocycles containing pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazole scaffold were synthesized from 1,3-dipolar cycloaddition reaction of pyrazolopyrimidinone based alkyne with azides using Cu(II) catalyst in presence of sodium ascorbate and evaluated for their anticancer efficacy in vitro against C6 rat and U87 human glioma cell lines. These compounds induced a concentration dependent inhibition of C6 rat and U87 human glioma cell proliferation. Compound 5f arrested the cells at S-phase of the cell cycle and induced apoptosis in U87 GBM cell lines. Further, apoptosis was evidenced by the cleavage of Caspase-3, PARP and up regulation of p53. In silico docking studies reveal that the compounds 5a, 5f and 5l were more effective in binding with TGFBR2 than other compounds.

Keywords: 1,2,3-Triazole; Anti-cancer activity; Apoptosis; Glioma; Pyrazolo[3,4-d]pyrimidin-4(5H)-one.