Dietary polyphenols rutin, taxifolin and quercetin related compounds target Leishmania amazonensis arginase

Author(s)

da Silva, Edson Roberto ^[1] ; Brogi, Simone ^{[2, 3, 4, 5]} ; Lucon-Junior, Joao Francisco ^[6] ; Campiani, Giuseppe ^{[2, 3]} ; Gemma, Sandra ^{[2, 3]} ; Maquiaveli, Claudia do Carmo ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Dept Med Vet, Ave Duque Caxias Norte 225, BR-13635900 Pirassununga, SP - Brazil

^[2] Univ Siena, European Res Ctr Drug Discovery & Dev NatSynDrugs, Via Aldo Moro 2, I-53100 Siena - Italy

^[3] Univ Siena, Dept Biotechnol Chem & Pharm, DoE Dept Excellence 2018 2022, Via Aldo Moro 2, I-53100 Siena - Italy

^[4] Univ Napoli Federico II, DoE Dept Excellence 2018 2022, Dept Pharm, Via D Montesano 49, I-80131 Naples - Italy

^[5] Univ Pisa, Dept Pharm, Via Bonanno 6, I-56126 Pisa - Italy

^[6] Univ Sao Paulo, Fac Zootecnia & Engn Alimentos, Programa Posgrad Biociencia Anim, BR-13635900 Pirassununga, SP - Brazil

• Document type: Journal article
• Source: FOOD & FUNCTION; v. 10, n. 6, p. 3172-3180, JUN 1 2019.
• Web of Science Citations: 0

Abstract

Quercetin related compounds were tested against Leishmania amazonensis arginase, a potential target for the development of new approaches in treating leishmaniasis. The IC50 and kinetic analysis were performed to determine the dissociation constant Ki and the inhibition mechanism of the parasite's arginase enzyme. The best arginase inhibition was obtained from taxifolin (dihydroquercetin) with IC50 = 1.6 +/- 0.1 mu M. This study showed for the first time that rutin (IC50 = 10.4 +/- 0.8 mu M), and human metabolite quercetin-3-O-glucuronide (IC50 = 8.2 +/- 0.4 mu M), target L. amazonensis arginase. In addition, computational studies applying molecular docking simulations were performed to gain insight into the molecular basis for arginase inhibition by the competitive inhibitors. Our results suggest that these compounds could be exploited to develop new approaches for treating leishmaniasis through molecular nutrition supplement in a drug-based therapy. (AU)

• FAPESP's process: 17/06917-4 - Study of the polyamine synthesis pathway and trypanothione synthesis for the development of new drugs for the treatment of leishmaniasis
• Grantee: Edson Roberto da Silva
• Support Opportunities: Regular Research Grants