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3-Hydroxynaphthalene-2-carboxanilides and their antitrypanosomal activity

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Abstract

Series of ring-substituted 3-hydroxynaphthalene-2-carboxanilides were screened for their in vitro activity against wild-type S427 (bloodstream form) of Trypanosoma brucei brucei. 3-Hydroxy-N-(3-trifluoromethylphenyl)- and 3-hydroxy-N-(4-trifluoromethylphenyl)naphthalene-2-carboxamides showed the highest biological activity (MIC = 1.56 and 2.08 µmol/dm3, respectively). Antitrypanosomal activity was correlated with the experimentally determined lipophilicity and acid–base dissociation constants of the compounds as well as with the calculated electronic properties of individual anilide substituents expressed as Hammett’s σ parameters. The substitution in the meta- or para-position of anilide of derivatives with higher lipophilicity by an electron-withdrawing moiety is favourable for higher activity. The optimum thermodynamic pK Ta value was found to be ca. 7.5. The structure–activity relationships of all compounds are discussed.

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Acknowledgements

This study was supported by Grants FaF UK/13/2016 and FaF UK/4/2017 and by sanofi-aventis Pharma Slovakia.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia

    Jiri Kos, Iva Kapustikova & Josef Jampilek

  2. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland, UK

    Carol Clements & Alexander I. Gray

Authors
  1. Jiri Kos
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  2. Iva Kapustikova
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  3. Carol Clements
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  4. Alexander I. Gray
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  5. Josef Jampilek
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Corresponding authors

Correspondence to Carol Clements or Josef Jampilek.

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Kos, J., Kapustikova, I., Clements, C. et al. 3-Hydroxynaphthalene-2-carboxanilides and their antitrypanosomal activity. Monatsh Chem 149, 887–892 (2018). https://doi.org/10.1007/s00706-017-2099-1

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  • DOI: https://doi.org/10.1007/s00706-017-2099-1

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