In-Depth In Silico Investigation Of Gitalin And Glaziovine As Possible VEGFR-2 Kinase Inhibitors For The Treatment Of Cancer

Abstract

Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) kinase inhibitors have been found to effectively suppress the process of angiogenesis or lymphangiogenesis, thereby exhibiting notable anticancer properties. In the current study, we have chosen two naturally occurring compounds, Gitalin and Glaziovine, as the focus of investigation. The objective is to assess their potential as inhibitors of VEGFR-2 kinase activity. Fro in silico ADMET analysis it was concluded that these compounds possess most favorable drug-likeness properties and can be treated as lead molecules for further analysis by molecular docking. Gitalin exhibited -8.3 kcal/mol of binding affinity and formed seven conventional, one carbon and one Pi-Donor hydrogen bond with Glu885, Asp1046, Arg1027, Glu885, Lys868 and Asp1028. It also displayed hydrophobic (Alkyl) Interactions with Leu1049, Lys868, Val914, Val916 and Ala881. Glaziovine displayed -8.1 kcal/mol and formed one carbon hydrogen bond with Glu885. It also showed Hydrophobic (Alkyl, Pi-Alkyl) Interactions with Met1016, Leu1019, Cys1024 and His1026. From molecular docking it was observed that both the compounds formed more stable complex than native ligand. Gitalin displayed formation of seven conventional hydrogen bonds with target which indicates it has potential to modulate the activity of target enzyme. This compound (Gitalin) can be tested further using in vitro and in vivo models for VEGFR-2 kinase activity to gather more quality data to claim its use clinically. Further lead optimization needed by applying numerous experimental techniques.