Design and synthesis of new 1,3,4-thiadiazoles as antimicrobial and antibiofilm agents.

Abstract

This study assessed the in vitro antibacterial and antibiofilm properties of new 1,3,4-thiadiazole derivatives. ¹H NMR and ¹³C NMR analyses were employed to confirm the structure of the synthesized compounds, the characterization is followed by assessments of their efficacy against Bacillus subtilis NRRL B478, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, as well as for antifungal activity against Candida albicans ATCC 90028 and Candida krusei ATCC 6258, using the broth microdilution method. Notably, among the tested compounds, compound 4a exhibited the highest antimicrobial activity, with a minimal inhibitory concentration of 125 μg/mL against P. aeruginosa ATCC 27853 and significant antibiofilm activity, achieving 94 %, 98 % and 100 % biofilm inhibition at 250, 500 and 1,000 μg/mL, respectively. Besides, compound 4h achieved 81 %, 89 % and 98 % S. aureus ATCC 29213 biofilm inhibition at 250, 500 and 1,000 μg/mL, respectively, and displayed potent antibacterial activity against this bacterium. Finally, the theoretical ADME properties of the compounds 4a-4h were analyzed by calculations. This study has consolidated a base for the development of new antibacterial and antibiofilm agents and advanced our understanding of their potential mode of action against biofilm-associated infections.