Inhibition of Leishmania -Epicatechin: A Comparative Structural Analysis of Enzyme-Inhibitor Interactions

• Published in: PloS one 2013-11, Vol.8 (11), p.e78387
• Main Authors: dos Reis, Matheus Balduíno Goncalves, Manjolin, Letícia Correa, Maquiaveli, Claudia do Carmo, Santos-Filho, Osvaldo Andrade, da Silva, Edson Roberto
• Format: Article
• Language: English
• Subjects: Catechin; Comparative analysis; Enzyme kinetics; Green tea; Leishmaniasis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0078387

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 (IC.sub.50 = 0.8 [micro]M) followed by (-)-epicatechin (IC.sub.50 = 1.8 [micro]M), gallic acid (IC.sub.50 = 2.2 [micro]M) and EGCG (IC.sub.50 = 3.8 [micro]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 IC.sub.50 values obtained for ARG-L, flavanols can be used as a supplement for leishmaniasis treatment.