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Arginase enzyme as a target to development of new prototype compound against Leishmania

Grant number: 14/18642-1
Support type:Regular Research Grants
Duration: March 01, 2015 - February 28, 2017
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal researcher:Edson Roberto da Silva
Grantee:Edson Roberto da Silva
Home Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
Assoc. researchers: Claudia Do Carmo Maquiaveli ; Paulo Cézar Vieira


The enzyme arginase of Leishmania is a validated target for the development of drugs against the parasite. Our group works with medicinal plants that possess leishmanicidal activity in culture of promastigote forms of the parasite and that simultaneously exhibit inhibitory activity of arginase enzyme in vitro. The study we conducted with medicinal plants showed that different flavonoids inhibit the enzyme arginase and have in vitro activity against promastigotes of L. (L.) amazonensis. Actives natural compounds tested against some species of Leishmania were identified as potential arginase inhibition of the parasite (IC50 4-10 uM). This study led us to the collaboration with the University of Siena, Italy: an initial screening of 20 synthetic compounds based on a natural inhibitor of arginase resulted in the identification of potent inhibitors (IC50 of 30 nM). The purpose of this project is to continue our studies with polyphenols and synthetic compounds from the database of compounds of University of Siena and others who will be synthesized. Furthermore we intend to construct a mutant arginase for expression of the stabilized protein in high concentrations to study crystallization parameters and crystallography. The purpose is identify the binding site of the non-competitive and uncompetitive inhibitors characterized previously. (AU)

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Scientific publications (4)
(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)
MAQUIAVELI, CLAUDIA DO CARMO; ROCHETTI, ARINA LAZARO; FUKUMASU, HEIDGE; VIEIRA, PAULO CEZAR; DA SILVA, EDSON ROBERTO. Antileishmanial activity of verbascoside: Selective arginase inhibition of intracellular amastigotes of Leishmania (Leishmania) amazonensis with resistance induced by LPS plus IFN-gamma. Biochemical Pharmacology, v. 127, p. 28-33, MAR 1 2017. Web of Science Citations: 4.
MAQUIAVELI, CLAUDIA DO CARMO; OLIVEIRA E SA, AMANDA MARIA; VIEIRA, PAULO CEZAR; DA SILVA, EDSON ROBERTO. Stachytarpheta cayennensis extract inhibits promastigote and amastigote growth in Leishmania amazonensis via parasite arginase inhibition. Journal of Ethnopharmacology, v. 192, p. 108-113, NOV 4 2016. Web of Science Citations: 5.
MAQUIAVELI, CLAUDIA C.; LUCON-JUNIOR, JOAO F.; BROGI, SIMONE; CAMPIANI, GIUSEPPE; GEMMA, SANDRA; VIEIRA, PAULO C.; SILVA, EDSON R. Verbascoside Inhibits Promastigote Growth and Arginase Activity of Leishmania amazonensis. Journal of Natural Products, v. 79, n. 5, p. 1459-1463, MAY 2016. Web of Science Citations: 13.
DA SILVA, EDSON R.; BOECHAT, NUBIA; PINHEIRO, LUIZ C. S.; BASTOS, MONICA M.; COSTA, CAROLINA C. P.; BARTHOLOMEU, JULIANA C.; DA COSTA, TALITA H. Novel Selective Inhibitor of Leishmania (Leishmania) amazonensis Arginase. CHEMICAL BIOLOGY & DRUG DESIGN, v. 86, n. 5, p. 969-978, NOV 2015. Web of Science Citations: 21.

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