In Silico Studies of N-(Phenyl Substituted) 2-([Phenyl Substituted) Methylidene] Amino)-N,4- Diphenyl-6h-1,3-Oxazin-6-Amine Derivatives as Potential Antibacterial Agents

Abstract

Resistance to bacteria is a growing threat to human health worldwide. The rate of discovery of new antibacterial is far outshined by the rate at which resistance is spreading. Therefore, there remains a pressing need for the development of new antibacterial drugs. Recent alarm estimates that deaths due to antimicrobial resistance may increase from 700,000 million lives annually by 2050. Glucosamine-6-phosphate (GlcN-6-P) synthase represents an interesting protein target because it plays an essential role in the protection of cell wall. The primary aim and objective of this study is to identify lead molecules as promising antibacterial agents by inhibiting Glucosamine-6-phosphate (GlcN-6-P) synthase enzyme. Autodock 4. 2, the effective tool for exploring the binding affinity of small molecule to enzyme target was used to study the interactions between the oxazine derivatives and the GlcN-6-P synthase binding site. The ligands were optimized for improving their efficacy and safety. Lead optimization was performed using Molinspiration server and the ligands were optimized for evaluating their oral bioavailability. With Glucosamine 6 phosphate synthase receptor, the binding energy was found to be best for 5 compounds SZ-3 (-5.27 kcal/mol), SZ-4 (-6.02 kcal/mol), SZ-5 (-5.35 kcal/mol), SZ-8 (-5.62kcal/mol), SZ-10 (-5.29 kcal/mol) when compared to the standard ligand, Ciprofloxacin (-5.09 kcal/mol) and were interacting well with the key residues TYR 304, GLU 438, LEU 484. Docking study strongly enhanced the activity of oxazine derivatives as new discovered hits.