Title:In Silico Identification of Novel Quinoline-3-carboxamide Derivatives
Targeting Platelet-Derived Growth Factor Receptor
Volume: 18
Issue: 2
Author(s): Ganesh S. Mhaske*, Ashim K. Sen, Ashish Shah, Rahul H. Khiste, Ajit V. Dale and Dhanya B. Sen
Affiliation:
- Department of Pharmacy, Sumandeep Vidyapeeth Deemed to be University, Vadodara-391760, Gujarat, India
- Indrayani Institute of Pharmaceutical Education and Research, Talegaon Dabhade, Pune-410507, Maharashtra, India
Keywords:
Molecular docking, PDGFRα, pharmacokinetics, H-bond, structure-based drug design, binding affinity.
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.
