Synthesis and Evaluation of Coumarin Clubbed Sulfanilamide and 2-Aminobenzothiazole Hybrids for Antibacterial Applications

Background: The increasing prevalence of drug-resistant bacterial infections poses a significant challenge to global healthcare, necessitating the development of novel antibacterial agents. Coumarin-based derivatives are well-recognized for their diverse biological activities, and hybridization with other pharmacophores offers a promising strategy for enhancing therapeutic efficacy and overcoming resistance.

Objective: This study aimed to synthesize and evaluate a novel series of coumarin hybrids by integrating the coumarin scaffold with sulfanilamide (9a-e) and 2-aminobenzothiazole (10a-e), targeting bacterial pathogens through a dual pharmacophoric approach.

Methods: The synthesized hybrids were characterized using mass spectrometry, FTIR, and NMR (1H and 13C) to confirm their structural integrity. Antibacterial activity was assessed in vitro against Escherichia coli and Staphylococcus aureus at concentrations of 100, 250, and 500 μg/ml, with ciprofloxacin as the standard. The molecular binding mechanism was explored using molecular docking and pharmacophore-based analysis.

Results: Among the synthesized derivatives, compounds 9e and 10e exhibited the highest antibacterial activity, with inhibition zones of 22 mm and 21 mm against E. coli and 25 mm and 22 mm against S. aureus at 500 μg/ml, demonstrating comparable efficacy to ciprofloxacin. Molecular docking studies revealed strong interactions of these compounds with bacterial enzymes, supporting the in vitro results and highlighting their potential as protein-inhibitor candidates.

Conclusion: The novel hybrid derivatives demonstrated significant antibacterial activities, suggesting their potential as promising therapeutic agents. Their effectiveness against various bacterial strains indicated that these compounds could serve as a foundation for the development of new antibacterial drugs. Further research and optimization are needed to enhance their potency and ensure their safety, paving the way for future clinical applications.