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Leishmania amazonensis Growth Inhibitors: Biological and Theoretical Features of Sulfonamide 4-Methoxychalcone Derivatives

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Abstract

Current drugs for treating leishmaniasis are still associated with significant toxicity and failure rates. Thus, new effective and less toxic antileishmanial agents are still in need. Herein, we tested a series of sulfonamide 4-methoxychalcone derivatives against L. amazonensis promastigote and amastigote forms to identify its antileishmanial profile against this species compared to L. braziliensis. In addition, we used molecular modeling tools to determine stereoelectronic features that may lead to the antileishmanial profile. Interestingly, all tested compounds were able to affect L. amazonensis promastigote form in a concentration-dependent manner and with low cytotoxicity, except for derivative 3g. However, our results showed that compound 3f (para-Cl) presents the best profile against both L. amazonensis forms (promastigote and amastigote), differently from that observed for L. braziliensis, when compound 3i was the most active. Structure–activity relationship (SAR) analysis of these derivatives pointed molecular volume, HOMO density, and conformational aspects as important characteristics for parasitic profile. Overall, sulfonamide 4-methoxychalcone derivatives may be pointed out not only as lead compounds for treating leishmaniasis (i.e., 3f) but also as experimental tools presenting parasite-selectivity (i.e., 3i).

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Acknowledgments

The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico/CNPq (Brazil), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Universidade Federal Fluminense (UFF) for the financial support.

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Authors and Affiliations

  1. ModMolQSAR, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, CEP 21941-590, Brazil

    Alessandra M. T. Souza, Uiaran Magalhães & Carlos R. Rodrigues

  2. LABioMol, GCM, Instituto de Biologia and Faculdade de Farmácia, Universidade Federal Fluminense (UFF), Niterói, RJ, CEP 24001-970, Brazil

    Alessandra M. T. Souza, Helena C. Castro & Dilvani O. Santos

  3. Faculdade de Farmácia, Universidade Federal Fluminense (UFF), Niterói, RJ, CEP 24001-970, Brazil

    Monique A. Brito

  4. Departamento de Química, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, Brazil

    Carla R. Andrighetti-Fröhner, Kely N. Oliveira, Antônio C. Joussef & Ricardo J. Nunes

  5. Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, Brazil

    Daniela Gaspar-Silva, Letícia K. Pacheco & Mário Steindel

  6. Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina (UFSC), Campus Universitário Trindade, Florianópolis, SC, Brazil

    Cláudia M. O. Simões

  7. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Ilha do Fundão, Cidade Universitária, Rio de Janeiro, RJ, 21941-909, Brazil

    Magaly G. Albuquerque

Authors
  1. Alessandra M. T. Souza
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  2. Helena C. Castro
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  3. Monique A. Brito
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  4. Carla R. Andrighetti-Fröhner
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  5. Uiaran Magalhães
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  8. Letícia K. Pacheco
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  9. Antônio C. Joussef
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  11. Cláudia M. O. Simões
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  12. Dilvani O. Santos
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  13. Magaly G. Albuquerque
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  14. Carlos R. Rodrigues
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  15. Ricardo J. Nunes
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Correspondence to Helena C. Castro.

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Souza, A.M.T., Castro, H.C., Brito, M.A. et al. Leishmania amazonensis Growth Inhibitors: Biological and Theoretical Features of Sulfonamide 4-Methoxychalcone Derivatives. Curr Microbiol 59, 374–379 (2009). https://doi.org/10.1007/s00284-009-9447-2

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  • DOI: https://doi.org/10.1007/s00284-009-9447-2

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