The increasing prevalence of antimicrobial resistance, particularly in Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), necessitates the development of novel therapeutic agents. In this study, an in silico approach was employed to design and evaluate Schiff’s base derivatives of quinoxaline-2,3-dione as potential next-generation antibiotics. A total of 41 derivatives were designed using rational drug design principles and assessed for drug-likeness using Lipinski’s rule of five, where all compounds demonstrated favorable properties. Molecular docking studies were performed against DNA gyrase (PDB ID: 2XCT) and MRSA protein (PDB ID: 6FTB) using AutoDock4. Several compounds exhibited superior binding affinity compared to standard drugs such as ciprofloxacin and streptomycin, indicating strong potential for antibacterial activity. ADMET analysis revealed that many derivatives showed good human intestinal absorption and acceptable pharmacokinetic profiles, although variations in permeability, metabolic stability, and toxicity were observed. Notably, some compounds demonstrated improved binding and pharmacokinetic characteristics with relatively lower cardiotoxicity risk. However, toxicity parameters such as hepatotoxicity and mutagenicity remain areas of concern. Overall, this study highlights quinoxaline derivatives as promising scaffolds and demonstrates the effectiveness of computer-aided drug design in accelerating the discovery of novel antibacterial agents against resistant pathogens.
Vani et al. (Mon,) studied this question.