Synthesis and in vitro cytotoxic activity of novel pyrazolo[3,4-d]pyrimidines and related pyrazole hydrazones toward breast adenocarcinoma MCF-7 cell line.

New series of pyrazolo[3,4-d]pyrimidines (7a-e and 13a-d) and pyrazole hydrazones 17a-d were synthesized and evaluated for their antiproliferative activity against human breast adenocarcinoma MCF-7 cell line. Most of the tested compounds exploited potent to moderate growth inhibitory activity, in particular compound 7e exhibited superior potency to the reference drug cisplatin (IC(50)=7.60 and 13.29 μM, respectively). The antitumor activity of the new compounds was accompanied by significant increase in the activity of superoxide dismutase with concomitant decrease in the activities of catalase and glutathione peroxidase and reduced glutathione level. Accordingly, the overproduction of hydrogen peroxide, nitric oxide and other free radicals allowed reactive oxygen species (ROS)-mediated tumor cells death, as monitored by reduction in the synthesis of protein and nucleic acids.