title: Exploring N-acylhydrazone derivatives against clinical resistant bacterial strains.
abstract: 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-NO(2), N-Br-FUR-NO(2), N-F-FUR-NO(2), N-Cl-FUR-NO(2)) 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.
authors.affiliation: Programa de Pós-Graduação em Patologia - HUAP, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil.
authors.forename: Andressa C
authors.initials: AC
authors.lastname: Lannes
authors.forename: Bruno
authors.initials: B
authors.lastname: Leal
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Novais
authors.forename: Viviane
authors.initials: V
authors.lastname: Lione
authors.forename: Georgia C T S
authors.initials: GC
authors.lastname: Monteiro
authors.forename: André L
authors.initials: AL
authors.lastname: Lourenço
authors.forename: Plínio C
authors.initials: PC
authors.lastname: Sathler
authors.forename: Alessandro K
authors.initials: AK
authors.lastname: Jordão
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Lúcio M
authors.initials: LM
authors.lastname: Cabral
authors.forename: Anna Claudia
authors.initials: AC
authors.lastname: Cunha
authors.forename: Vinicius
authors.initials: V
authors.lastname: Campos
authors.forename: Vítor F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Maria Cecília B V
authors.initials: MC
authors.lastname: de Souza
authors.forename: Dilvani O
authors.initials: DO
authors.lastname: Santos
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000382:microbiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D006835:Hydrazones