Synthesis and anticancer effects of some novel pyrazolo[3,4- d]pyrimidine derivatives by generating reactive oxygen species in human breast adenocarcinoma cells

Abstract

A series of novel substituted pyrazolo[3,4- d]pyrimidines (compounds 2– 12) were synthesized starting with pyrimidinone derivative 1. Their in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cell lines has been investigated and most of the tested compounds exploited potent cytotoxic activity against MCF-7 cell lines comparable to the activity of the commonly used anticancer drug cisplatin. Treatment of MCF-7 cells with increased doses (2, 5, 10, 20 μg/ml) of the tested compounds revealed that the activity of superoxide dismutase and the level of hydrogen peroxide were significantly increased, while the activities of catalase and glutathione peroxidase and the levels of reduced glutathione were significantly lowered compared with control MCF-7 cells. In general, acyclic nucleoside derivative 4 revealed the highest anticancer activity among the other tested compounds.