Inhibition of Leishmania (Leishmania) amazonensis and Rat Arginases by Green Tea EGCG, (+)-Catechin and (2)-Epicatechin: A Comparative Structural Analysis of Enzyme-Inhibitor Interactions

Autor(es)

Goncalves dos Reis, Matheus Balduino ^[1] ; Manjolin, Leticia Correa ^[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, Pirassununga, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Fisiol, Programa Posgrad Fisiol, BR-14049 Ribeirao Preto, SP - Brazil

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

^[4] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Dept Vet Med, Pirassununga, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 11 NOV 8 2013.
• Citações Web of Science: 27

Resumo

Epigallocatechin-3-gallate (EGCG), a dietary polyphenol (flavanol) from green tea, possesses leishmanicidal and antitrypanosomal activity. Mitochondrial damage was observed in Leishmania treated with EGCG, and it contributed to the lethal effect. However, the molecular target has not been defined. In this study, EGCG, (+)-catechin and (2)-epicatechin were tested against recombinant arginase from Leishmania amazonensis (ARG-L) and rat liver arginase (ARG-1). The compounds inhibit ARG-L and ARG-1 but are more active against the parasite enzyme. Enzyme kinetics reveal that EGCG is a mixed inhibitor of the ARG-L while (+)-catechin and (2)-epicatechin are competitive inhibitors. The most potent arginase inhibitor is (+)-catechin (IC50 = 0.8 mu M) followed by (2)-epicatechin (IC50 = 1.8 mu M), gallic acid (IC50 = 2.2 mu M) and EGCG (IC50 = 3.8 mu M). Docking analyses showed different modes of interaction of the compounds with the active sites of ARG-L and ARG-1. Due to the low IC50 values obtained for ARG-L, flavanols can be used as a supplement for leishmaniasis treatment. (AU)

• 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