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Synthesis, biological evaluation and molecular docking studies of 3-(triazolyl)coumarin derivatives: Effect on inducible nitric oxide synthase

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Autor(es):
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Stefani, Helio A. [1] ; Gueogjan, Karina [1] ; Manarin, Flavia [1] ; Farsky, Sandra H. P. [2] ; Zukerman-Schpector, Julio [3] ; Caracelli, Ignez [4] ; Pizano Rodrigues, Sergio R. [5] ; Muscara, Marcelo N. [6] ; Teixeira, Simone A. [6] ; Santin, Jose R. [2] ; Machado, Isabel D. [2] ; Bolonheis, Simone M. [2] ; Curi, Rui [7] ; Vinolo, Marco A. [7]
Número total de Autores: 14
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Farm, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo - Brazil
[3] Univ Fed Sao Carlos, Dept Quim, BR-13560 Sao Carlos, SP - Brazil
[4] Univ Fed Sao Carlos, Dept Fis, BioMat, BR-13560 Sao Carlos, SP - Brazil
[5] Univ Fed Sao Carlos, Programa Posgrad Biotecnol, BR-13560 Sao Carlos, SP - Brazil
[6] Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508 Sao Paulo - Brazil
[7] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol, BR-05508 Sao Paulo - Brazil
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 58, p. 117-127, DEC 2012.
Citações Web of Science: 39
Resumo

A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-alpha secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that it pi center dot center dot center dot pi interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored. (C) 2012 Elsevier Masson SAS. All rights reserved. (AU)

Processo FAPESP: 10/15677-8 - Síntese de Estirenos alfa-Substituídos
Beneficiário:Flávia Giovana Manarin
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 07/59404-2 - Reações entre sais de potássio de organotrifluoroboratos e espécies eletrofílicas de telúrio e haletos orgânicos
Beneficiário:Helio Alexandre Stefani
Modalidade de apoio: Auxílio à Pesquisa - Temático