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Exploring N-Acylhydrazone Derivatives Against Clinical Resistant Bacterial Strains

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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–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.

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Acknowledgments

We thank the support of Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal Docente (CAPES), and Pro-reitoria de Pesquisa e Inovação da Universidade Federal Fluminense (PROPPi-UFF) for the financial support and fellowships.

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Authors and Affiliations

  1. Programa de Pós-Graduação em Patologia - HUAP, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    Andressa C. Lannes, Bruno Leal & André L. Lourenço

  2. Programa de Pós-Graduação em Ciências e Biotecnologia, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    Juliana S. Novais, Georgia C. T. S. Monteiro, Dilvani O. Santos & Helena C. Castro

  3. Laboratório de Modelagem Molecular e QSAR (ModMolQSAR-3D), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Viviane Lione, Plínio C. Sathler, Carlos R. Rodrigues & Lúcio M. Cabral

  4. Programa de Pós-Graduação em Química - IQ, Universidade Federal Fluminense, Niterói, Rio de Janeiro, Brazil

    Alessandro K. Jordão, Anna Claudia Cunha, Vinicius Campos, Vítor F. Ferreira & Maria Cecília B. V. de Souza

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  1. Andressa C. Lannes
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  2. Bruno Leal
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  3. Juliana S. Novais
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  8. Alessandro K. Jordão
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  9. Carlos R. Rodrigues
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  10. Lúcio M. Cabral
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  11. Anna Claudia Cunha
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  14. Maria Cecília B. V. de Souza
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  15. Dilvani O. Santos
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  16. Helena C. Castro
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Correspondence to Helena C. Castro.

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Lannes, A.C., Leal, B., Novais, J.S. et al. Exploring N-Acylhydrazone Derivatives Against Clinical Resistant Bacterial Strains. Curr Microbiol 69, 357–364 (2014). https://doi.org/10.1007/s00284-014-0591-y

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