Synthesis, antimicrobial activity and in silico studies of novel sulfonamide-benzothiazole conjugate compounds

Abstract

The emergence of multidrug-resistant pathogens and polymicrobial infections underscores the urgent need for novel broad-spectrum antimicrobial agents. In this study, a series of sulfonamide–benzothiazole conjugates (4a–4j) were synthesized via a straightforward, scalable route employing thioamide formation, nucleophilic substitution, and Schiff base condensation. Structural characterization was confirmed by ^1H NMR, EI-MS, FTIR, and elemental analysis. Antimicrobial activity was evaluated against Gram-positive ( Staphylococcus aureus, Bacillus subtilis ), Gram-negative ( Escherichia coli, Pseudomonas aeruginosa ), and fungal strains ( Aspergillus niger, Candida albicans ) using the Kirby–Bauer disk diffusion assay. Several derivatives, notably 4c, 4d, 4i, and 4j, exhibited significant inhibition zones comparable to standard drugs, demonstrating broad-spectrum efficacy. In silico ADME profiling using SwissADME revealed favorable lipophilicity (LogP 4.75–7.48) and acceptable TPSA values (120.40–212.04 Ų), suggesting good membrane permeability and oral bioavailability. Although most compounds violated two Lipinski’s rules (molecular weight and molar refractivity), compound 4a satisfied four criteria, indicating promising drug-likeness. These findings highlight sulfonamide–benzothiazole hybrids as potential scaffolds for developing multifunctional antimicrobial agents with enhanced pharmacokinetic properties.