Avaliação da atividade antibacteriana e citotóxica de compostos de tiossulfonatos

Abstract

Bacterial resistance is one of the most pressing challenges in global public health, driving the search for new molecules with antimicrobial potential. In this study, seven synthetic thiosulfonates were synthesized, structurally characterized by spectroscopic techniques (¹H and ¹³C NMR, HRMS), and evaluated for their antibacterial and cytotoxic activities. The compounds 4- MBMT, 4-MBET, and 4-MBAT showed the most promising results in disk diffusion, MIC, and MBC assays, effectively inhibiting both Gram-positive and Gram-negative bacterial strains, including multidrug-resistant clinical isolates (S. aureus, E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii). MIC values ranged from 0.093 to 0.744 mg/mL, and MBC data confirmed the bactericidal effect. Time-kill assays demonstrated rapid and efficient bacterial elimination, with complete colony reduction within 6 hours at the highest tested concentrations. To assess biological safety, hemolysis and cytotoxicity assays (MTT and neutral red uptake) were performed. None of the compounds caused significant hemolysis at any concentration, indicating low toxicity toward erythrocytes. In MTT assays, the IC₅₀ values were 0.0784 mg/mL (4-MBAT), 0.0218 mg/mL (4-MBET), and 0.0207 mg/mL (4-MBMT). In the neutral red assay, the IC₅₀ values were 0.097 mg/mL, 0.022 mg/mL, and 0.0075 mg/mL, respectively. Although cytotoxicity was observed at concentrations close to those required for antimicrobial activity, the findings support the potential of these molecules as candidates for therapeutic development, especially in the context of increasing bacterial resistance. This study is the first to report the use of the neutral red assay in the evaluation of thiosulfonates and emphasizes the need for formulation strategies to reduce cytotoxicity. The results highlight thiosulfonates as promising structures for the development of new antimicrobial agents.