Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide derivatives.

ABSTRACT: The study presented here aimed at identifying a new class of compounds acting against Leishmania parasites, the causative agent of Leishmaniasis. For this purpose, the thioether derivatives of our in-house library have been evaluated in whole-cell screening assays in order to determine their in vitro activity against Leishmania protozoan. Among them, promising results have been achieved with compound RDS 777 (6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine) (IC₅₀=29.43 µM), which is able to impair the mechanism of the parasite defence against the reactive oxygen species by inhibiting the trypanothione reductase (TR) with high efficiency (K_i 0.25 ± 0.18 µM). The X-ray structure of L. infantum TR in complex with RDS 777 disclosed the mechanism of a

SUBMITTER: Saccoliti F 

PROVIDER: S-EPMC6010130 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature