Study of the polyamine synthesis pathway and trypanothione synthesis for the development of new drugs for the treatment of leishmaniasis

• Grant number: 17/06917-4
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2017
• End date: July 31, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Edson Roberto da Silva
• Grantee: Edson Roberto da Silva
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated researchers: Claudia do Carmo Maquiaveli

Abstract

In the last five years our group has described the interaction of natural and synthetic compounds with the enzyme arginase of Leishmania amazonensis. The first natural compound discovered was quercetin, followed by a synthetic compound containing a thiosemicarbazide functional group. These studies described for the first time the selective inhibition of L. amazonensis arginase. Recently, we have shown that the natural verboscoside compound also selectively inhibits L. amazonensis arginase. Verbascoside is an abundant compound in the medicinal plant Stachytarpheta cayennensis used in the Brazilian Amazon for treatment of cutaneous leishmaniasis. This work was the first to describes the mechanism of action of S. cayennensis extract showing that arginase was inhibited in the promastigotes and amastigotes forms of L. amazonensis. Using L. amazonensis arginase inhibitors already described and others that may be discovered we intend to verify if the parasite alters the expression of the enzymes of the polyamine synthesis pathway, the expression of the cationic L-arginine transporter and the expression of trypanothione synthase and trypanothione Reductase. In addition, trials of new synthetic drugs designed as arginase inhibitors will be continued to develop a new treatment of leishmaniasis. (AU)

Scientific publications

(5)

(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)

DA SILVA, EDSON ROBERTO; BROGI, SIMONE; LUCON-JUNIOR, JOAO FRANCISCO; CAMPIANI, GIUSEPPE; GEMMA, SANDRA; MAQUIAVELI, CLAUDIA DO CARMO. Dietary polyphenols rutin, taxifolin and quercetin related compounds target Leishmania amazonensis arginase. FOOD & FUNCTION, v. 10, n. 6, p. 3172-3180, JUN 1 2019. (17/06917-4)

FEITOSA, LIVIA M.; DA SILVA, EDSON R.; HOELZ, LUCAS V. B.; SOUZA, DANIELLE L.; COME, JULIO A. A. S. S.; CARDOSO-SANTOS, CAMILA; BATISTA, MARCOS M.; SOEIRO, MARIA DE NAZARE C.; BOECHAT, NUBIA; PINHEIRO, LUIZ C. S.. New pyrazolopyrimidine derivatives as Leishmania amazonensis arginase inhibitors. Bioorganic & Medicinal Chemistry, v. 27, n. 14, p. 3061-3069, JUL 15 2019. (17/06917-4)

COME, JULIO ABEL ALFREDO DOS SANTOS SIMONE; ZHUANG, YIBIN; LI, TIANZHEN; BROGI, SIMONE; GEMMA, SANDRA; LIU, TAO; DA SILVA, EDSON ROBERTO. In Vitro and In Silico Analyses of New Cinnamid and Rosmarinic Acid-Derived Compounds Biosynthesized in Escherichia coli as Leishmania amazonensis Arginase Inhibitors. PATHOGENS, v. 11, n. 9, p. 14-pg., 2022-09-01. (17/06917-4)

DE LIMA, EVANOEL CRIZANTO; CASTELO-BRANCO, FREDERICO S.; MAQUIAVELI, CLAUDIA C.; FARIAS, ANDRE B.; RENNO, MAGDALENA N.; BOECHAT, NUBIA; SILVA, EDSON R.. Phenylhydrazides as inhibitors of Leishmania amazonensis arginase and antileishmanial activity. Bioorganic & Medicinal Chemistry, v. 27, n. 17, p. 3853-3859, SEP 1 2019. (17/06917-4)

DA SILVA, EDSON ROBERTO; BROGI, SIMONE; GRILLO, ALESSANDRO; CAMPIANI, GIUSEPPE; GEMMA, SANDRA; VIEIRA, PAULO CEZAR; MAQUIAVELI, CLAUDIA DO CARMO. Cinnamic acids derived compounds with antileishmanial activity target Leishmania amazonensis arginase. CHEMICAL BIOLOGY & DRUG DESIGN, v. 93, n. 2, p. 139-146, FEB 2019. (17/06917-4)