Interaction of Some Amino-Nitrile Derivatives with Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) Using a Theoretical Model.

Background: Some studies indicate that the angiogenesis process is related to vascular endothelial growth factor, which can interact with endothelial cell surface receptors (VEGF-R1, VEGF-R2, and VEGF-R3); this biochemical process and other factors result in the promotion and growth of new blood vessels under normal conditions. However, some studies indicate that this phenomenon could also occur in cancer cells. It is important to mention that some amino derivatives have been prepared as VEGF-R1 inhibitors; however, their interaction with VEGF-R1 is not clear, perhaps due to different experimental approaches or differences in their chemical structure.

Objective: The aim of this study was to evaluate the theoretical interaction of several amino-nitrile derivatives (Compounds 1 to 38) with VEGF-R1.

Methods: The theoretical interaction of amino-nitrile derivatives with VEGF-R1 was carried out using the 3hng protein as the theoretical model. In addition, cabozantinib, pazopanib, regorafenib, and sorafenib were used as controls in the DockingServer program.

Results: The results showed different amino acid residues involved in the interaction of amino-nitrile derivatives with the 3hng protein surface compared with the controls. In addition, the inhibition constant (Ki) was lower for Compounds 10 and 34 than for cabozantinib. Other results show that Ki for Compounds 9, 10, 14, 27-29 and 34-36 was lower in comparison with pazopanib, regorafenib, and sorafenib.

Conclusions: All theoretical data suggest that amino-nitrile derivatives could produce changes in the growth of some cancer cell lines through VEGFR-1 inhibition. Therefore, these amino-nitrile derivatives could be a therapeutic alternative to treat some types of cancer.