MOLECULAR DOCKING STUDY OF QUINOLIN-4(1H)-ONE DERIVATIVES AS VEGFR-2 INHIBITORS FOR THE TREATMENT OF LUNG CANCER

Abstract

A tyrosine kinase receptor (TKR), vascular endothelial growth factor receptor-2 (VEGFR-2), is often overexpressed in the majority of tumors. It is essential for tumor angiogenesis because it mediates important angiogenic biological signals, such as vascular permeability, endothelial cell survival, migration and proliferation. VEGFR-2 has become an acceptable therapeutic target against cancer because of its critical role in facilitating tumor vasculature. Inhibiting the VEGF signaling pathways has emerged as a useful cancer therapeutic strategy. This study designed and developed a variety of quinolin-4(1H)-one derivatives that are strong inhibitors of VEGFR-2 (KDR) kinase. These substances were developed with a urea moiety and quinoline scaffold, and their biological activity against VEGFR-2 was examined. The compound with the most inhibitory action on VEGFR-2 was Q2. The preliminary pharmacophoric hypothesis was validated by docking data, which also indicated a common mechanism of interaction at the ATP-binding site of VEGFR-2. This suggests that substance Q2 is a promising cancer therapeutic drug that deserves further research.

The Quinolone scaffold was initially discovered to have antimicrobial properties, and its derivatives were found to have a variety of pharmacological activity, such as anticancer properties. Derivatives of quinolin-4(H)-one have been found to block a number of proteins and enzymes, including phosphoinositide 3-kinases (PI3K), that are implicated in the proliferation of cancer cells. Quinolones have also been investigated as EGFR and VEGFR protein kinase inhibitor.

Using auto dock vina, discovery studio, and PyMol, we examined the molecular interactions of 10 bioactive compounds against VEGFR-2 in present work. In the docking test, the chosen quinolin-4(H)-one derivatives showed good inhibitory action with target proteins. The binding interactions' affinities range from -14.65 to -11.31 Kcal/mol, and the chosen hits' docking result is similar to that of regular sorafenib. Of all the compounds that were examined, Q2 had the highest docking score, Q6 the lowest binding interaction against VEGFR-2.