The discovery of new potent VEGFR2 inhibitors for potential anti-angiogenesis agent through a combination of structure-based virtual screening, molecular dynamics simulation and ADME-Tox prediction

Year 2024, , 48 - 61, 02.12.2024

Hanane Boucherıt , Amina Merzoug , Ilham Boulhıssa , Asma Mosbah , Abderrahmane Benseguenı

https://doi.org/10.33435/tcandtc.1437517

Abstract

The discovery of the importance of angiogenesis in the mechanisms of tumor growth has empowered the improvement of new particles that are utilized in the therapy of various cancers. The goal of this research was to identify novel compounds functioning as potent VEGFR2 inhibitors in silico. It is an interesting therapeutic target for developing new anti-angiogenic drugs. In this work, molecular simulation studies of enzyme inhibition was carried out by structure-based virtual screening with FlexX program of VEGFR2. This approach makes it possible to model the interactions between a protein and thousands of small chemical compounds. A collection of 6,000 compounds originating from the ZINC chemical library, were tested against the active site of VEGFR2. The ADME-Tox characteristics and molecular dynamics simulation of the potential compounds were also examined. At the end of this screening, the compounds ZINC01534124 and ZINC00588595 appear as new inhibitors theoretically more active towards VEGFR2. Again, these inhibitors have shown significant binding energy by interacting with important residues in the active site. Furthermore, the in silico prediction of a similar drug positively informs us about the ADME-Tox properties of these new compounds. Finally, the stable binding of VEGFR2 with ZINC01534124 and ZINC00588595 is shown using 100 ns molecular dynamics simulations. These findings point to the chemicals ZINC01534124 and ZINC00588595 as potential candidates for VEGFR2 inhibitor research. They might also act as a starting point for further chemical modifications in order to produce therapeutically relevant anti-angiogenic medications.

Keywords

VEGFR2, Anti-angiogenic, virtual screening, molecular dynamics simulation, ADMETox

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