Investigation of benzothiazole-Schiff bases for antimicrobial activities through ADMET, Molecular Docking, and DFT analysis

Abstract

Antimicrobial resistance is a critical global issue necessitating new antimicrobial agents. This study investigates four benzothiazole-Schiff base hybrids known for their antibacterial properties, utilizing a computational framework that includes Density Functional Theory (DFT), molecular docking, and ADMET profiling. DFT analysis revealed that the hybrids have lower HOMO-LUMO energy gaps (4.05 to 4.11 eV) and higher electrophilicity indices compared to ciprofloxacin, indicating greater reactivity, which correlates with their low Minimum Inhibitory Concentrations (MICs: 3.91 to 15.6 µg/mL). Molecular docking studies confirmed strong binding affinities, especially for compounds S19 and S15, which interact effectively through hydrogen bonding and hydrophobic interactions within the active site of bacterial enzyme targets (S. aureus Gyrase B, S. typhi Gyrase A, E. coli Gyrase). Notably, ADMET profiling identified S19 as the leading candidate due to its favourable safety profile, being non-mutagenic and free from hERG cardiotoxicity risks. This comprehensive study offers detailed atomic-level insights into the antimicrobial mechanisms of benzothiazole-Schiff base hybrids, with S19 standing out as a promising lead compound for further experimental antibiotic development.