DESIGNING AND VIRTUAL SCREENING OF QUINAZOLINONE ANALOGUES AS POTENTIAL PHARMACOPHORES FOR ANTITUBERCULAR ACTIVITY

Abstract

Drug-resistant infections, particularly Mycobacterium tuberculosis, have increased dramatically in recent years, necessitating the discovery and development of novel antimycobacterial drugs. Quinazolinone derivatives are widely utilized in the pharmaceutical industry and medicine for a variety of biological activities including antiinflammatory, antibacterial, antioxidant, anticancer, and antihypertensive effects. The goal of this study is to use the VLife MDS software package, version 3.0, to conduct G-QSAR and docking investigations on a series of 2, 3- substituted quinazoline-4(3H)-one for antitubercular activity. The compounds were chosen based on their expected activity from the G-QSAR model, and molecular docking research was used to verify and identify their affinity for the DNA gyrase protein. 52 molecules in a series of 2, 3- substituted quinazoline-4(3H)-one were subjected to GQSAR, which allows flexibility to study molecular substitution sites. With different QSAR model studies (2D, 3D, and G), we designed and predicted new chemical entities i.e. NCE’s which were screened by Lipinski’s rule of five. The lowest MIC compounds in the series and NCEs were docked onto a DNA gyrase protein, and the docking score was compared to that of the standard medication sparfloxacin