Design, synthesis, <i>in silico</i> studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers
Abdulrahman M. Saleh, Hazem A. Mahdy, Mohamed Ayman El‐Zahabi, Ahmed B. M. Mehany, Mohamed M. Khalifa, Ibrahim H. Eissa
Abstract
values of 0.61 and 0.53 μM, respectively, compared to sorafenib. Bedsides, compound 11e arrested the HCT-116 cell growth at S and sub-G1 phases, induced a significant increase in the apoptotic cells, and caused remarkable decrease in the levels of TNF-α, IL-6, and caspase-3. Finally, the binding patterns of the target derivatives were investigated through the docking study against the proposed molecular target (VEGFR-2, PDB ID 1YWN). The results of molecular docking studies showed similar binding modes to sorafenib against VEGFR-2. In addition, molecular dynamic simulations revealed the stability of compound 11e in the active site for 100 ns.