Antimicrobial Evaluation of 5-Substituted Aryl 1H-Tetrazoles

Background: Tetrazole derivatives such as 1-substituted dinitrobenzyl tetrazoles and their oxa and selanyl analogs have previously been studied against drug-susceptible and multidrugresistant mycobacteria. In addition, other tetrazole derivatives have been shown to inhibit CTX-M class A β-lactamases. Objective: To study the antibacterial activity of 5-substituted aryl 1H-tetrazole derivatives. Methods: The antibacterial activity of several known 5-substituted aryl 1H-tetrazole derivatives was evaluated against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The activity was assessed by determining the minimum inhibitory concentration of these tetrazole derivatives and comparing them to the known antibiotics amoxicillin, trimethoprim and sulfamethoxazole. Results: Some derivatives showed significant antibacterial activity with the most active derivatives exhibiting a minimum inhibitory concentration (MIC) of 125-250 μg/mL against Staphylococcus aureus and Escherichia coli. Using some of these tetrazole compounds in combination with trimethoprim led to a synergistic effect that gave MIC values ranging from 0.24-1.95 μg/mL against Escherichia coli and 3.91-31.3 μg/mL against Staphylococcus aureus. The tetrazole derivatives were prepared in an isopropanol/water mixture using microwave heating at 160 oC for 1h. The cycloaddition between organonitriles and sodium azide was catalyzed by indium chloride. Conclusion: This study shows a significant synergistic effect between the tetrazole compounds tested and trimethoprim which could be used to potentially develop new antibacterial agents.