Molecular Docking Study of Novel Isatin-Niflumic Acid Derivatives as Possible VEGFR Tyrosine Kinase Inhibitors

Abstract

Designing and evaluating six novel isatin-niflumic acid derivatives as a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2). Since there is overexpression of VEGFR-2 in aggressive malignancies, including glioblastoma, hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and non-small cell lung cancer (NSCLC), this overexpression leads to dysregulated angiogenesis and uncontrolled cellular growth. Inhibiting VEGFR-2 kinase active site (PDB code: 4AG8) is a critical target in developing anticancer medications, as it can aid in the prevention of tumor growth and metastasis through blocking phosphorylation cascades required for endothelial cell proliferation and utilizing the molecular operating environment to assess the binding affinity of novel design compounds against targeting proteins (VEGFR-2) kinase active site. The docking outcomes depend on two important parameters, S-score and RMSD, for investigating molecular interactions and drug discovery. The newly designed compounds (I-VI) exhibit improved binding energy (S.score) ranging from -9.1782 to -9.5120 Kcal/mol and reduced RMSD values ranging from 1.0608 to 1.8914 with the enzyme active site with additional four to five binding interactions, in comparison to Sunitinib binding energy of -8.7276 Kcal/mol and RMSD value of 2.0611 and only exhibit two binding interactions with the active site. These results suggest that the newly designed compounds have the potential to be effective VEGFR-2 tyrosine kinase inhibitors when compared to the reference ligand (Sunitinib).