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

This study assessed the <i>in vitro</i> 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 <i>Bacillus subtilis</i> NRRL B478, <i>Staphylococcus aureus</i> ATCC 29213, <i>Escherichia coli</i> ATCC 25922, <i>Pseudomonas aeruginosa</i> ATCC 27853, as well as for antifungal activity against <i>Candida albicans</i> ATCC 90028 and <i>Candida krusei</i> ATCC 6258, using the broth microdilution method. Notably, among the tested compounds, compound <b>4a</b> exhibited the highest antimicrobial activity, with a minimal inhibitory concentration of 125 μg/mL against <i>P. aeruginosa</i> ATCC 27853 and significant antibiofilm activity, achieving 94 %, 98 % and 100 % biofilm inhibition at 250, 500 and 1,000 μg/mL, respectively. Besides, compound <b>4h</b> achieved 81 %, 89 % and 98 % <i>S. aureus</i> 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 <b>4a</b>-<b>4h</b> 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.