Prediction of ADME/Tox properties, 2D,3D QSAR and molecular docking approach of 2,3‐disubstituted‐Quinazolin‐4(3H)‐ones using X‐ray crystal structure of Staphylococcus aureus (1T2W) Sortase A

Abstract

AbstractNew chemical entities of quinazolinone derivatives were used to design as antibacterial agents through selective inhibitors of X‐ray crystal structure of Staphylococcus aureus (1T2W) sortase A by the molecular docking using V‐Life Sciences MDS version 4.6, software. It is successfully reproduced the binding approach of the crystal structure of the Staphylococcus aureus antagonists. The docking results suggested that the modification in the series that gives better binding potential, hydrophobic Van der Waals, H‐bond and charge interactions are responsible for forming the stable compounds of the ligands with receptor. It has been observed that the ligands numbers 4k, 4l, and 4m possess a minimum docking score i.e. minimum binding energy in kilocalorie per mole i.e. these molecules have more affinity for active site of receptor. 2D and 3D QSAR analyses were carried out on quinazoline‐4‐one derivatives for their antimicrobial activities on S. aureus. The activity of the molecules was transformed into log 1/C. The statistically significant of 2DQSAR and 3D QSAR models are r2 = 0.8066 and q2 = 0.6789 and internal (q2 = 0.7157) and external (predictive r2 = 0.4634), respectively. This study revealed that the major contributing descriptors of 2D QSAR studies are DeltaEpsilonB and DeltaPsiA and 3D QSAR model proves the steric as well as electrostatic effects determine the binding affinity for the drug development. The results of the current computational studies are useful for further designing novel chemical entities of anti‐microbial agent.