3-Hydroxykynurenine, a Tryptophan Metabolite Generated During the Infection, Is Active Against

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2017 Jul 26

PMID 28740612

Citations 9

Authors

Carolina P Knubel

Constanza Insfran

Fernando F Martinez

Cintia Diaz Lujan

Ricardo E Fretes

Martin G Theumer

Laura Cervi

Claudia C Motran

Affiliations

Soon will be listed here.

Abstract

The antiparasitic activity of 3-hydroxykynurenine (3-HK), one of the major tryptophan catabolites of the kynurenine pathway, against both evolutive forms that are important for human infection, trypomastigotes (Tps) and amastigotes (Am), possible targets in the parasite and the drug toxicity to mammalian cells have been investigated. 3-HK showed a potent activity against Am with IC values in the micromolar concentration range, while the IC values to cause Tps death was ∼6000-times higher, indicating that the replicative form present in the vertebrate hosts is much more susceptible to 3-HK than bloodstream Tps. In addition, 3-HK showed activity against Tps and Am, at concentrations that did not exhibit toxicity to mammalian cells. Ultrastructural analysis and flow cytometry studies indicated that Am and Tps mitochondrion and nuclei contain 3-HK targets. The potency and selectivity of 3-HK, which is generated during infection in human and mice, suggest that 3-HK may be a suitable candidate for drug research and development for Chagas disease.

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