Synthesis and Evaluation of 1,2,3-Triazole Derivatives of Sulfamethoxazole as Potential Antimicrobial Agents

Mohammed A. Dakhil ¹, Mustafa Kadhum Naeem ², Farked Wahoodi Salman ³, Ali Jabbar Radhi ^4*

Novel sulfamethoxazole derivatives incorporating 1,2,3-triazole moieties showed promise as antimicrobial agents against multidrug-resistant bacteria.

Abstract

Background: Sulfamethoxazole, a commonly used antibiotic, has faced challenges due to emerging resistant bacterial strains. Recent efforts have focused on synthesizing sulfamethoxazole derivatives incorporating 1,2,3-triazole heterocycles, known for their diverse pharmacological activities. Methods: The synthesis of azido sulfamethoxazole and its subsequent transformation into 1,2,3-triazole derivatives (1t, 2t, and 3t) were achieved through copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. Characterization of synthesized compounds was performed using FT-IR and NMR spectroscopy. Antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated using the diffusion method on Mueller-Hinton agar. Molecular docking studies were conducted to predict interactions between synthesized compounds and bacterial proteins. Results: Successful synthesis of azido sulfamethoxazole and 1,2,3-triazole derivatives was confirmed through spectroscopic analyses. The derivatives exhibited promising antibacterial activity against both Gram-negative and Gram-positive bacteria, with some compounds showing synergistic effects when combined with existing antibiotics. Molecular docking studies revealed potential binding interactions between the synthesized compounds and bacterial proteins. Conclusion: The study demonstrated the effective synthesis of novel sulfamethoxazole derivatives incorporating 1,2,3-triazole heterocycles, exhibiting significant antibacterial activity.

Keywords: Antimicrobial resistance, Sulfamethoxazole derivatives, 1,2,3-Triazole heterocycles, Click chemistry, Antibacterial activity

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