Dietary flavonoids fisetin, luteolin and their derived compounds inhibit arginase, a central enzyme in Leishmania (Leishmania) amazonensis infection

Autor(es)

Manjolin, Leticia Correa ^[1] ; Goncalves dos Reis, Matheus Balduino ^[1] ; Maquiaveli, Claudia do Carmo ^[2] ; Santos-Filho, Osvaldo Andrade ^[3] ; da Silva, Edson Roberto ^[4]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Programa Iniciacao Cient, BR-13635900 Pirassununga, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Fisiol, Programa Posgrad Fisiol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Farmanguinhos Fundacao Oswald Cruz, Dept Sintese Organ, Lab Modelagem Mol, BR-21041250 Rio De Janeiro, RJ - Brazil

^[4] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Lab Imunol Parasitas, BR-13635900 Pirassununga, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Food Chemistry; v. 141, n. 3, p. 2253-2262, DEC 1 2013.
• Citações Web of Science: 44

Resumo

Fisetin, quercetin, luteolin and 7,8-hydroxyflavone show high activity in Leishmania cultures and present low toxicity to mammalian cells. In this work, the structural aspects of 13 flavonoids were analyzed for their inhibition of the arginase enzyme from Leishmania (Leishmania) amazonensis. A higher potency of arginase inhibition was observed with fisetin, which was four and ten times greater than that of quercetin and luteolin, respectively. These data show that the hydroxyl group at position 3 contributed significantly to the inhibitory activity of arginase, while the hydroxyl group at position 5 did not. The absence of the catechol group on apigenin drastically decreased arginase inhibition. Additionally, the docking of compounds showed that the inhibitors interact with amino acids involved in the Mn+2 - Mn+2 metal bridge formation at the catalytic site. Due to the low IC50 values of these flavonoids, they may be used as a food supplement in leishmaniasis treatment. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 09/08715-3 - Novos alvos terapêuticos: utilização de enzimas recombinantes para triagem de fármacos de interesse médico veterinário e humano.
• Beneficiário: Edson Roberto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/17059-5 - Caracterização de inibidores naturais e estudo da relação estrutura-atividade de flavonóides isolados sobre a enzima arginase de Leishmania amazonensis
• Beneficiário: Edson Roberto da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular