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Morita-Baylis-Hillman adduct shows in vitro activity against Leishmania (Viannia) braziliensis associated with a reduction in IL-6 and IL-10 but independent of nitric oxide

Published online by Cambridge University Press:  04 August 2012

F. M. AMORIM ,
Y. K. S. RODRIGUES ,
T. P. BARBOSA ,
P. L. N. NÉRIS ,
J. P. A. CALDAS ,
S. C. O. SOUSA ,
J. A. LEITE ,
S. RODRIGUES-MASCARENHAS ,
M. L. A. A. VASCONCELLOS  and
M. R. OLIVEIRA
F. M. AMORIM
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Departamento de Biologia Molecular, Laboratório Biologia de Leishmania, João Pessoa, Paraíba, Brazil
Y. K. S. RODRIGUES
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Departamento de Biologia Molecular, Laboratório Biologia de Leishmania, João Pessoa, Paraíba, Brazil
T. P. BARBOSA
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Departamento de Química, Laboratório de Síntese Orgânica Medicinal, João Pessoa, Paraíba, Brazil
P. L. N. NÉRIS
Affiliation:
Universidade Federal da Paraíba, Departamento de Biologia Molecular, Laboratório Biologia de Leishmania, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brazil
J. P. A. CALDAS
Affiliation:
Universidade Federal da Paraíba, Departamento de Biologia Molecular, Laboratório Biologia de Leishmania, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brazil
S. C. O. SOUSA
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Departamento de Química, Laboratório de Síntese Orgânica Medicinal, João Pessoa, Paraíba, Brazil
J. A. LEITE
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Centro de Biotecnologia, Laboratório de Imunofarmacologia, João Pessoa, Paraíba, Brazil
S. RODRIGUES-MASCARENHAS
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Centro de Biotecnologia, Laboratório de Imunofarmacologia, João Pessoa, Paraíba, Brazil
M. L. A. A. VASCONCELLOS
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Departamento de Química, Laboratório de Síntese Orgânica Medicinal, João Pessoa, Paraíba, Brazil
M. R. OLIVEIRA*
Affiliation:
Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Departamento de Biologia Molecular, Laboratório Biologia de Leishmania, João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brazil
*
*Corresponding author: Laboratório Biologia de Leishmania, Departamento de Biologia Molecular, Centro de Ciências Exatas e da Natureza, Universidade Federal da Paraíba, Campus I, Castelo Branco, João Pessoa, Paraíba, Brasil, CEP 58059-900. Tel: +55 83 3216 7436. E-mail: [email protected]
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Summary

Current treatments for different clinical forms of leishmaniasis are unsatisfactory, highly toxic and associated with increasing failure rates resulting from the emergence of resistant parasites. Leishmania (Viannia) braziliensis is the main aetiological agent of different clinical forms of American tegumentary leishmaniasis, including the mucosal form for which treatment has high failure rates. The aim of this work was to investigate the activity of the Morita-Baylis-Hillman adduct, methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate in vitro against isolates of L. (V.) braziliensis obtained from patients with different clinical manifestations of tegumentary leishmaniasis: localized cutaneous leishmaniasis, mucosal leishmaniasis and disseminated cutaneous leishmaniasis. The adduct effectively inhibited the growth of promastigotes of the different isolates of L. (V.) braziliensis (IC50 ⩽ 7·77 μg/ml), as well as reduced the infection rate of macrophages infected with these parasites (EC50 ⩽ 1·37 μg/ml). It is remarkable to state that the adduct was more effective against intracellular amastigotes (P ⩽ 0·0045). The anti-amastigote activity correlated with an immunomodulatory effect, since the adduct was able to decrease the production of IL-6 and IL-10 by the infected macrophages. However, its effect was independent of nitric oxide production. This work demonstrates the anti-leishmanial activity of methyl 2-{2-[hydroxy(2-nitrophenyl)methyl])acryloyloxy} benzoate and suggests its potential in the treatment of human infections caused by L. (V.) braziliensis.

Keywords

Leishmania (Viannia) braziliensisMorita-Baylis-Hillman adductmacrophageIL-6IL-10nitric oxide
Type
Research Article
Information
Parasitology , Volume 140 , Issue 1 , January 2013 , pp. 29 - 38
Copyright
Copyright © Cambridge University Press 2012

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