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Synthesis of piplartine analogs and preliminary findings on structure–antimicrobial activity relationship

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Abstract

In this work it is described the synthesis, characterization and antimicrobial and toxicity evaluation of a series of analogs of piplartine, a piperamide found in Piper sp. The compounds structures were confirmed by infrared spectroscopy, 1H, 13C nuclear magnetic resonance, high resolution mass spectroscopy and were evaluated against strains of Candida spp., Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Derivative 24 was almost four-fold more potent (IC50: 48.83 μM) and five-fold less toxic (SI > 3) than piplartine (IC50: 189.2 μM; SI: 0.21) against Candida krusei, as well as two-fold more potent than fluconazole (IC50: 104.48 μM). This compound was also active against Candida tropicalis at 97.67 μM. Benzoyl derivative 17 was three-fold more potent (IC50: 85.2 μM) and more than five-fold less toxic (CC50: 231.71 μM) than piplartine (IC50: 315.33 μM and CC50: 41.14 μM) against Staphylococcus aureus. Given these findings, we have found analogs of piplartine which can be assumed as prototypes for the optimization and the development of new antimicrobial (compounds 24 and 17) agents.

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Acknowledgments

This work was supported by FAPEMIG (APQ-01209-13), CAPES, CNPq and FINEP.

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Authors and Affiliations

  1. Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, 37130-000, MG, Brazil

    Antonio Maciel Fregnan & Diogo Teixeira Carvalho

  2. Instituto de Química, Universidade Federal de Alfenas, Alfenas, 37130-000, MG, Brazil

    Guilherme Andrade Brancaglion, Danielle Ferreira Dias & Thiago Belarmino de Souza

  3. Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rio de Janeiro, 40296-710, BA, Brazil

    Alexandre Francisco Cerqueira Galvão, Cinara Oliveira D’Sousa Costa, Diogo Rodrigo Magalhães Moreira, Milena Botelho Pereira Soares & Daniel Pereira Bezerra

  4. Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, São Marcos, 41253-190, BA, Brazil

    Diogo Rodrigo Magalhães Moreira & Milena Botelho Pereira Soares

  5. Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, 37130-000, MG, Brazil

    Naiara Chaves Silva, Stella Maria de Souza Morais, Josidel Conceição Oliver, Amanda Latercia Tranches Dias & Luiz Felipe Leomil Coelho

Authors
  1. Antonio Maciel Fregnan
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  2. Guilherme Andrade Brancaglion
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  3. Alexandre Francisco Cerqueira Galvão
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  9. Stella Maria de Souza Morais
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  10. Josidel Conceição Oliver
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  11. Amanda Latercia Tranches Dias
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  12. Luiz Felipe Leomil Coelho
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  13. Diogo Teixeira Carvalho
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  14. Danielle Ferreira Dias
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  15. Thiago Belarmino de Souza
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Correspondence to Thiago Belarmino de Souza.

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Fregnan, A.M., Brancaglion, G.A., Galvão, A.F.C. et al. Synthesis of piplartine analogs and preliminary findings on structure–antimicrobial activity relationship. Med Chem Res 26, 603–614 (2017). https://doi.org/10.1007/s00044-016-1774-9

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  • DOI: https://doi.org/10.1007/s00044-016-1774-9

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