DEVELOPMENT AND STRUCTURAL ELUCIDATION OF NOVEL AZOMETHINE DERIVATIVES WITH POTENT ANTIMICROBIAL PROFILES: AN IN-SILICO MOLECULAR DOCKING AND ADMET STUDY

Abstract

The therapeutic efficacy of existing antimicrobial agents is severely challenged by the global rise of multidrug-resistant pathogens. Azomethine derivatives (Schiff bases) represent a crucial class of pharmacophores with extensive biological applicability. In this study, a series of novel substituted azomethine analogs (AZ-1 to AZ-6) were computationally evaluated through molecular docking against bacterial DNA Gyrase (PDB ID: 1KZN) alongside comprehensive pharmacokinetic (ADMET) profiling using SwissADME parameters. Molecular docking simulations demonstrated strong binding affinities ranging from -6.9 to -8.4 kcal/mol. Notably, electron-withdrawing substituents—specifically the 3,4-dichloro derivative (AZ-4, -8.4 kcal/mol) and the 4-nitro derivative (AZ-2, -8.1 kcal/mol)—exhibited superior active site interactions compared to electron-donating analogs. Pharmacokinetic screening verified zero violations of Lipinski's Rule of Five across all molecules, confirming high gastrointestinal absorption and excellent drug-likeness profiles. These findings provide a compelling rationalization for utilizing substituted azomethine scaffolds in targeted antibacterial drug development.[1]