ZnO Nanoparticles Catalyst in the Synthesis of Bioactive Fused Pyrimidines as Anti-breast Cancer Agents Targeting VEGFR-2

Background: Pyrimidines emerged as a remarkable class of heterocyclic compounds that have reinforced the pharmaceutical chemistry with various bioactive antitumor agents. Moreover, pyrimidine scaffold displayed VEGFR-2 inhibitory activity. Also, nano-sized catalysts are used in organic reactions in order to speed up the catalytic process. Objective: We were interested herein to synthesize a new series of fused pyrimidines using ZnO(NPs) to investigate their antitumor efficiency against breast MCF7 cancer and their VEGFR-2 inhibition properties. Method: A simple and efficient method for the synthesis of fused pyrimidines was developed using zinc oxide nanoparticles ZnO(NPs) in refluxing ethanol. Results: The proposed structures of all new fused pyrimidines arc in agreement with their spectral data. Antitumor evaluation of newly fused pyrimidine derivatives against breast MCF-7 cancer was performed. It was apparent that the 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a (IC50 = 9.121.+/- 16 mu g/ml), 9c (IC50 = 9.10 +/- 1.07 mu g/ml) and 9d (IC50 = 9.60 +/- 1.22 mu g/ml) exhibited equipotent antitumor activity as Tamoxifen (IC50 = 9.11 +/- 0.90 mu g/ml). Also, the inhibitory activity of the novel fused pyrimidine derivatives on VEGFR-2 as well as Tamoxifen was determined using breast cancer cell line MCF-7. The data was obvious that 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a, 9c and 9d exhibited noticeable VEGFR-2 inhibitory effect with % inhibition ranging from 80-84 % versus Tamoxifen 93.5%. Conclusion: We succeeded in this context to synthesize new fused pyrimidines using ZnO(NPs) as anti-breast cancer agents targeting VEGFR-2.