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Exploring N-Acylhydrazone Derivatives Against Clinical Resistant Bacterial Strains

Lannes, Andressa C., Leal, Bruno, Novais, Juliana S., Lione, Viviane, Monteiro, Georgia C. T. S., Lourenço, André L., Sathler, Plínio C., Jordão, Alessandro K., Rodrigues, Carlos R., Cabral, Lúcio M., Cunha, Anna Claudia, Campos, Vinicius, Ferreira, Vítor F., de Souza, Maria Cecília B. V., Santos, Dilvani O., Castro, Helena C.
Current microbiology 2014 v.69 no.3 pp. 357-364
Gram-negative bacteria, antimicrobial properties, ciprofloxacin, cytotoxicity, humans, macrophages, models, nitrofurans, risk, risk profile, toxicology, vancomycin
Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N–H–FUR–NO₂, N–Br–FUR–NO₂, N–F–FUR–NO₂, N–Cl–FUR–NO₂) showed promising MIC and MBC values (MIC = MBC = 1–16 μg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.