title: Dietary flavonoids fisetin, luteolin and their derived compounds inhibit arginase, a central enzyme in Leishmania (Leishmania) amazonensis infection.
abstract: Fisetin, quercetin, luteolin and 7,8-hydroxyflavone show high activity in Leishmania cultures and present low toxicity to mammalian cells. In this work, the structural aspects of 13 flavonoids were analyzed for their inhibition of the arginase enzyme from Leishmania (Leishmania) amazonensis. A higher potency of arginase inhibition was observed with fisetin, which was four and ten times greater than that of quercetin and luteolin, respectively. These data show that the hydroxyl group at position 3 contributed significantly to the inhibitory activity of arginase, while the hydroxyl group at position 5 did not. The absence of the catechol group on apigenin drastically decreased arginase inhibition. Additionally, the docking of compounds showed that the inhibitors interact with amino acids involved in the Mn(+2)-Mn(+2) metal bridge formation at the catalytic site. Due to the low IC50 values of these flavonoids, they may be used as a food supplement in leishmaniasis treatment.
authors.affiliation: Programa de Iniciação Científica da Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo, Av. Duque de Caxias Norte, 225, Pirassununga, SP 13635-900, Brazil.
authors.forename: Leticia Correa
authors.initials: LC
authors.lastname: Manjolin
authors.forename: Matheus Balduíno Goncalves
authors.initials: MB
authors.lastname: dos Reis
authors.forename: Claudia do Carmo
authors.initials: Cdo C
authors.lastname: Maquiaveli
authors.forename: Osvaldo Andrade
authors.initials: OA
authors.lastname: Santos-Filho
authors.forename: Edson Roberto
authors.initials: ER
authors.lastname: da Silva
mesh_terms: D001119:Arginase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry*; D044948:Flavonols; D006801:Humans; D007700:Kinetics; D007891:Leishmania / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D007896:Leishmaniasis / Q000469:parasitology; D047311:Luteolin / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D044948:Flavonols; D015800:Protozoan Proteins; D001119:Arginase; D047311:Luteolin; C017875:fisetin
keywords: Arginase; Flavonoid; Leishmania; Polyamines; Polyphenols; ROS