Design of Novel Naphthalimidopropanediol Derivatives as Staphylococcus Aureus Antibacterial Agents Utilizing 3D‐QSAR, ADMET, Molecular Docking, and Dynamics Simulations

Abstract

Staphylococcus aureus is a prevalent foodborne pathogen, and its resistance has become more pronounced due to antibiotic overuse. In this paper, we constructed a 3D‐QSAR model using 47 naphthalimidopropanediols derivatives (NIOLs). The results indicate that the CoMFA model (q2 = 0.771, r2 = 0.998) and CoMSIA‐ASH model (q2 = 0.638, r2 = 0.995) exhibit favorable predictive capabilities, leading to the design of 11 novel NIOLs as antibacterial agents. ADMET was used to validate their pharmacokinetic characteristics, molecular docking was performed to validate the binding capability of the designed molecules, dynamics simulations, and binding free energy were employed to verify the accuracy of docking results. The results demonstrate excellent performance of the designed novel molecules, which may provide significant references for the development of novel and effective antibacterial agents against S. aureus.