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Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)

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Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Nat. Prod. 2021, 84, 6, 1787-1798
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    Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)
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    • Anderson Dematei
      Anderson Dematei
      Center for Tropical Medicine, NMT, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      More by Anderson Dematei
    • João B. Nunes
      João B. Nunes
      Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      Laboratory for the Synthesis and Analysis of Biomolecules, LSAB, Institute of Chemistry, University of Brasilia, Brasília 70910-900, Brazil
      More by João B. Nunes
    • Daniel C. Moreira
      Daniel C. Moreira
      Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      More by Daniel C. Moreira
      Orcidhttps://orcid.org/0000-0003-1961-7281
    • Jéssica A. Jesus
      Jéssica A. Jesus
      Institute of Biosciences, São Paulo State University, São Paulo, Brazil
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    • Márcia D. Laurenti
      Márcia D. Laurenti
      Department of Pathology, Laboratory of Pathology of Infectious Diseases, Faculty of Medicine, University of São Paulo, São Paulo 05508-060, Brazil
      More by Márcia D. Laurenti
    • Ana C. A. Mengarda
      Ana C. A. Mengarda
      Research Center on Neglected Diseases, NPDN, University of Guarulhos, Guarulhos 07023-070, Brazil
      More by Ana C. A. Mengarda
    • Maria Silva Vieira
      Maria Silva Vieira
      I3S, Institute of Research and Innovation in Health, University of Porto, Porto 4099-002, Portugal
      IBMC, Institute of Molecular and Cellular Biology, University of Porto, Porto 4099-002, Portugal
      More by Maria Silva Vieira
    • Constança Pais do Amaral
      Constança Pais do Amaral
      Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
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    • Marco M. Domingues
      Marco M. Domingues
      Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
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    • Josué de Moraes
      Josué de Moraes
      Research Center on Neglected Diseases, NPDN, University of Guarulhos, Guarulhos 07023-070, Brazil
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      Orcidhttps://orcid.org/0000-0003-1766-7031
    • Luiz F. D. Passero
      Luiz F. D. Passero
      Institute of Biosciences, São Paulo State University, São Paulo, Brazil
      Department of Pathology, Laboratory of Pathology of Infectious Diseases, Faculty of Medicine, University of São Paulo, São Paulo 05508-060, Brazil
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    • Guilherme Brand
      Guilherme Brand
      Laboratory for the Synthesis and Analysis of Biomolecules, LSAB, Institute of Chemistry, University of Brasilia, Brasília 70910-900, Brazil
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      Orcidhttps://orcid.org/0000-0002-1615-0009
    • Lucinda J. Bessa
      Lucinda J. Bessa
      LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, Porto 4099-002, Portugal
      More by Lucinda J. Bessa
    • Reinhard Wimmer
      Reinhard Wimmer
      Department of Chemistry and Bioscience, Aalborg University, Aalborg 9220, Denmark
      More by Reinhard Wimmer
      Orcidhttps://orcid.org/0000-0001-6942-5056
    • Selma A. S. Kuckelhaus
      Selma A. S. Kuckelhaus
      Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      More by Selma A. S. Kuckelhaus
    • Ana M. Tomás
      Ana M. Tomás
      I3S, Institute of Research and Innovation in Health, University of Porto, Porto 4099-002, Portugal
      IBMC, Institute of Molecular and Cellular Biology, University of Porto, Porto 4099-002, Portugal
      ICBAS, Abel Salazar Institute for Biomedical Research, University of Porto, Porto 4099-002, Portugal
      More by Ana M. Tomás
    • Nuno C. Santos
      Nuno C. Santos
      Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal
      More by Nuno C. Santos
    • Alexandra Plácido
      Alexandra Plácido
      LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, Porto 4099-002, Portugal
      More by Alexandra Plácido
    • Peter Eaton
      Peter Eaton
      LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Porto, Porto 4099-002, Portugal
      The Bridge, Joseph Banks Laboratories, School of Chemistry, University of Lincoln, Lincoln LN6 7TS, U.K.
      More by Peter Eaton
    • José Roberto S. A. Leite*
      José Roberto S. A. Leite
      Center for Tropical Medicine, NMT, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      Research Center in Morphology and Applied Immunology, NuPMIA, Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      *Phone: +556131071891. E-mail: [email protected]; [email protected]
      More by José Roberto S. A. Leite
      Orcidhttps://orcid.org/0000-0002-1096-3236
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    Journal of Natural Products

    Cite this: J. Nat. Prod. 2021, 84, 6, 1787–1798
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.1c00153
    Published June 2, 2021
    Copyright © 2021 American Chemical Society and American Society of Pharmacognosy
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    Abstract

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    Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

    Copyright © 2021 American Chemical Society and American Society of Pharmacognosy

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    Journal of Natural Products

    Cite this: J. Nat. Prod. 2021, 84, 6, 1787–1798
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.1c00153
    Published June 2, 2021
    Copyright © 2021 American Chemical Society and American Society of Pharmacognosy
    Request reuse permissions

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