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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

4 `-Aminochalcones As Novel Inhibitors of the Chlorinating Activity of Myeloperoxidase

Texto completo
Autor(es):
Zeraik, M. L. [1] ; Ximenes, V. F. [2] ; Regasini, L. O. [1] ; Dutra, L. A. [1] ; Silva, D. H. S. [1] ; Fonseca, L. M. [3] ; Coelho, D. [4] ; Machado, S. A. S. [4] ; Bolzani, V. S. [1]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Sao Paulo State Univ UNESP, Dept Organ Chem, Inst Chem, Nuclei Bioassays Ecophysiol & Biosynth Nat Prod N, BR-14800900 Sao Paulo - Brazil
[2] Sao Paulo State Univ UNESP, Fac Sci, Dept Chem, BR-17033360 Sao Paulo - Brazil
[3] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, BR-14801902 Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Chem, BR-13560970 Sao Carlos, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo de Revisão
Fonte: Current Medicinal Chemistry; v. 19, n. 31, p. 5405-5413, NOV 2012.
Citações Web of Science: 26
Resumo

The excessive activation of neutrophils generates reactive oxygen species (ROS) and the secretion of primary granular enzymes, such as myeloperoxidase (MPO), which is implicated in numerous inflammatory diseases. The aim of this study was to evaluate chalcones as inhibitors of the chlorinating activity of MPO using in vitro and ex vivo assays. In addition to cytotoxic properties, the inhibition of respiratory burst, the scavenger capacity, and the oxidation potential were measured. 4'-Aminochalcone (1), 4'-amino-4-fluorochalcone (2), and 4'-amino-4-methylchalcone (3) exhibited potent inhibition of the chlorinating activity of MPO, as evaluated in a neutrophil system and a free cell system, to the following degree: (1) IC50 = 0.265 +/- 0.036 mu ol L-1; (2) IC50 = 0.250 +/- 0.081 mu ol L-1; and (3) IC50 = 0.250 +/- 0.012 mu ol L-1. These values were similar to those for 5-fluorotryptamine (IC50 = 0.192 +/- 0.012 mu ol L-1), a compound considered to be a potent MPO inhibitor. These aminochalcones were not toxic to neutrophils at concentrations below 100 mu ol L-1, as determined by the trypan blue exclusion assay. Compounds 1-3 presented a high oxidation potential (E-pa1 approximate to 0.80 V), low scavenger capacity against DPPH center dot and HOCl, and low inhibition of respiratory burst. These data indicated that aminochalcones are potent inhibitors of MPO chlorinating activity, a new property for chalcone derivatives, given that they are neither antioxidant agents nor inhibitors of respiratory burst. In conclusion, the selected aminochalcones have potential as pharmacological agents for inflammatory diseases. (AU)

Processo FAPESP: 11/03017-6 - Produtos naturais oriundos de plantas do Cerrado e Mata Atlântica, modelos potenciais e úteis para identificar protótipos com ação oxidante em neutrófilos e enzima mieloperoxidase (MPO)
Beneficiário:Maria Luiza Zeraik
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 10/52327-5 - Prospecção de moléculas bioativas e estudo de variabilidade infra-específica em plantas e microorganismos endófitos do cerrado e caatinga: contribuição para o conhecimento e uso sustentável da biodiversidade brasileira
Beneficiário:Vanderlan da Silva Bolzani
Linha de fomento: Auxílio à Pesquisa - Programa BIOTA - Regular