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

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 μM. This study showed for the first time that rutin (IC₅₀ = 10.4 ± 0.8 μM), and human metabolite quercetin-3-O-glucuronide (IC₅₀ = 8.2 ± 0.4 μM), 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.