In Silico Identification of Novel Quinoline-3-carboxamide Derivatives Targeting Platelet-Derived Growth Factor Receptor

Abstract

Background: Several computer-aided drug design (CADD) methods enable the design and development of novel chemical entities. Structure-based drug design (SBDD) and the knowledge of in silico methods enable the visualization of the binding process of ligands to targets and to predict the key binding pocket sites and affinity of ligands to their target macromolecules. Objective: The present study was carried out to identify novel N-2-amino-N-phenyl quinoline-3- carboxamide (AQCMs) derivatives targeting Platelet-derived growth factor receptor (PDGFR) to cure cancer using in silico approach. Materials and Methods: AQCMs were designed using ChemAxon Marvin Sketch 5.11.5 software. SwissADME and admetSAR online webserver were used to predict physicochemical properties as well as the toxicity of compounds. Ligand-receptor interactions between quinoline-3-carboxamide derivatives with the target receptor (PDB: 5GRN) were carried out using molecular docking technique by employing various software like AutoDock 1.1.2, MGL Tools 1.5.6, Discovery Studio Visualizer v 20.1.0.19295, Procheck, ProtParam tool, and PyMOL. Results: In silico results reveal that all designed compounds had acceptable pharmacokinetic properties, were found to be orally bioavailable, and less harmful. Molecules from 36 to 39 showed better docking scores as compared to standard drugs sunitinib and tasquinimod. Conclusion: Increase in binding energy and the number of H-bonds established by AQCMs with below 3.40 Å distance interactions allows a valuable starting point in order to optimize compounds for further investigation. Pharmacokinetics and toxicological profile build up the applicability of quinoline-3-carboxamide moiety as a potential new candidate for the cure of cancer that could help the medicinal chemists for additional extensive in vitro, in vivo chemical, and pharmacological investigations.