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Characterization of natural inhibitors and the study of structure-activity relationship of flavonoids based on the arginase enzyme from Leishmania amazonensis


Leishmaniasis is a anthropozoonosis that affects domestic dogs and humans. The dogs with leishmaniasis are sacrificed due to lack of proper treatment. The enzyme arginase of Leishmania is a validated target for developing drugs against the parasite. Our group works with medicinal plants that have activity in cultured parasite and inhibit the enzyme arginase. The plant Cecropia pachystachya has in vitro activity against promastigotes of L. (L.) amazonensis arginase and inhibits the parasite arginase enzyme. We have recently shown that quercetin and derivatives compounds (quercitrin and isoquercitrin) are inhibitors of arginase (IC50 4-10 µM). Some flavonoids were tested by our group and showed inhibitory activity of the enzyme arginase. So this project we propose a study of structure activity relationship of flavonoids on the inhibition of the enzyme arginase, verification of the mechanism of action in cultured promastigotes by supplementation with ornithine or putrescine. In addition, we propose to continue the study of plants showing simultaneous activity against Leishmania and inhibition of arginase for the screening of new inhibitors. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MANJOLIN, LETICIA CORREA; GONCALVES DOS REIS, MATHEUS BALDUINO; MAQUIAVELI, CLAUDIA DO CARMO; SANTOS-FILHO, OSVALDO ANDRADE; DA SILVA, EDSON ROBERTO. Dietary flavonoids fisetin, luteolin and their derived compounds inhibit arginase, a central enzyme in Leishmania (Leishmania) amazonensis infection. Food Chemistry, v. 141, n. 3, p. 2253-2262, . (09/08715-3, 12/17059-5)
GONCALVES DOS REIS, MATHEUS BALDUINO; MANJOLIN, LETICIA CORREA; MAQUIAVELI, CLAUDIA DO CARMO; SANTOS-FILHO, OSVALDO ANDRADE; DA SILVA, EDSON ROBERTO. Inhibition of Leishmania (Leishmania) amazonensis and Rat Arginases by Green Tea EGCG, (+)-Catechin and (2)-Epicatechin: A Comparative Structural Analysis of Enzyme-Inhibitor Interactions. PLoS One, v. 8, n. 11, . (12/17059-5)
MAQUIAVELI, CLAUDIA C.; DA SILVA, EDSON R.; ROSA, LARA C.; FRANCESCATO, HELOISA D. C.; LUCON JUNIOR, JOAO FRANCISCO; SILVA, CLEONICE G. A.; CASARINI, DULCE E.; RONCHI, FERNANDA A.; COIMBRA, TEREZILA M.. Cecropia pachystachya extract attenuated the renal lesion in 5/6 nephrectomized rats by reducing inflammation and renal arginase activity. Journal of Ethnopharmacology, v. 158, n. A, p. 49-57, . (12/17059-5)

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