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 are 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 =
9.12±1.16 μg/ml), 9c (IC50 = 9.10±1.07 μg/ml) and 9d (IC50 = 9.60±1.22 μg/ml) exhibited equipotent
antitumor activity as Tamoxifen (IC50 = 9.11±0.90 μg/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.