Synthesis of Some Novel Pyrazolo[3,4-d] pyrimidine Derivatives and Evaluation of their Invitro Antiproliferative and Antioxidant Activity

Aymn E. Rashad; Samir T Gaballa; Ahmed I Hashem; Dalia Ahmed A Osman; Mamdouh M Ali; Said Fatouh Hamed; Farouk ME Abdel-Megeid

Abstract

Synthesis of Some Novel Pyrazolo[3,4-d] pyrimidine Derivatives and Evaluation of their Invitro Antiproliferative and Antioxidant Activity

Author(s): Aymn E. Rashad, Samir T Gaballa, Ahmed I Hashem, Dalia Ahmed A Osman, Mamdouh M Ali , Said Fatouh Hamed, Farouk ME Abdel-Megeid*

Novel substituted pyrazolo[3,4-d]pyrimidines 4-27 were synthesized starting with 1-substituted-5-amino-1Hpyrazole- 4-carbonitrile 1. Some of the prepared compounds were tested for their anticancer as well as antioxidant activities. As anticancer agents, the tested compounds were evaluated for their antiproliferative potency and their effects on the free-radical-metabolizing enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). The levels of the oxidative stress parameters including hydrogen peroxide (H2O2), nitric oxide (NO) and reduced glutathione (GSH) were also investigated in vitro on human breast (MCF-7), liver (HepG2) and lung (A549) cancer cell lines comparing with the reference anticancer drug cisplatin. The antioxidant ability of the tested compounds was measured by evaluating their radical scavenging ability (RSA%) using DPPH and ABTS radical scavenging assays. Results indicated that most of the compounds exhibited remarkable cytotoxicity activity against MCF-7 and A549 cell lines. For MCF-7 cell line, the IC50 of N-[(9-methyl-5,6- dihydronaphtho[1',2':4,5]thieno[2,3-d]pyrimidin-11-yl)]-1H-pyrazolo[3,4-d]pyrimidin-4-yl)ethane-1,2-diamine 11 (IC50: 3.60 μg/mL) was found to be more potent and efficacious than cisplatin (IC50: 4.70 μg/mL). The value of A- 549 cell line IC50 of 1-(9-methyl-5,6-dihydronaphtho[1',2':4,5]thieno[2,3-d]pyrimidin-11-yl)-6-phenyl-1,5,- dihydropyrazolo[3,4-d]pyrimidin-4-one 22 (IC50 4.80 μg/mL) is close to that of cisplatin (IC50: 3.65 μg/mL). The antitumor activity of these compounds was accompanied with high activity of SOD with subsequent increase in H2O2 and NO production. All the selected compounds gave positive RSA % either by DPPH or ABTS assays.

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