title: Inhibition of Leishmania (Leishmania) amazonensis and rat arginases by green tea EGCG, (+)-catechin and (-)-epicatechin: a comparative structural analysis of enzyme-inhibitor interactions.
abstract: 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 (-)-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 (-)-epicatechin are competitive inhibitors. The most potent arginase inhibitor is (+)-catechin (IC50 = 0.8 µM) followed by (-)-epicatechin (IC50 = 1.8 µM), gallic acid (IC50 = 2.2 µM) and EGCG (IC50 = 3.8 µM). 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.
authors.affiliation: Programa de Iniciação Científica da Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Pirassununga, São Paulo, Brazil.
authors.forename: Matheus Balduíno Goncalves
authors.initials: MB
authors.lastname: dos Reis
authors.forename: Letícia Correa
authors.initials: LC
authors.lastname: Manjolin
authors.forename: Claudia do Carmo
authors.initials: Cdo C
authors.lastname: Maquiaveli
authors.forename: Osvaldo Andrade
authors.initials: OA
authors.lastname: Santos-Filho
authors.forename: Edson Roberto
authors.initials: ER
authors.lastname: da Silva
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D007891:Leishmania / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D062105:Molecular Docking Simulation; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: D016588:Anticarcinogenic Agents; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D002392:Catechin; C045651:epigallocatechin gallate; D001119:Arginase