Antibacterial activity, molecular docking, and in silico safety profiling of novel 3,10-dihydro-2H-1,3-oxazepino[7,6-b]indole derivatives

Abstract

In this study, nine derivatives of 3,10-dihydro-2 H -1,3-oxazepino[7,6- b ]indole (1–9), which combine two bioactive pharmacophoric cores, were synthesized and tested for antibacterial activity against five pathogenic bacterial strains. The resazurin-based microdilution plate method was used to determine minimum inhibitory concentration (MIC) values. Derivative 6 displayed the greatest potency (MIC = 0.0048 mg/mL against S. typhimurium ). Molecular docking suggested possible interactions between the ligands and peptidoglycan glycosyltransferases. In silico analysis using SwissADME, ProTox 3.0, Cytotoxicity Predictor Online, quantitative structure–activity relationship (QSAR), and quantitative structure–activity/toxicity (QSAT) modeling suggested high gastrointestinal absorption, adherence to drug-likeness rules, and low predicted cytotoxicity across 198 human cell lines. Toxicological predictions suggested nontoxic behavior of all derivatives, with lower predicted activity in normal fibroblasts than in tumor-derived lines. The findings identify derivative 6 as the most active antibacterial candidate and derivative 5 as a safe lead with balanced antimicrobial potential, supporting further antibacterial drug research and the development of these scaffolds for clinical application.