Amino acid and polyamine membrane transporters in Trypanosoma cruzi: biological function and evaluation as drug targets

SAYE M; REIGADA C; GAUNA L; VALERA VERA EA; PEREIRA CA; MIRANDA MR

CURRENT MEDICINAL CHEMISTRY.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2019

0929-8673

Amino acids and polyamines are involved in relevant processes for the parasite Trypanosoma cruzi, like protein synthesis, stress resistance, life cycle progression, infection establishment and redox balance, among others. In addition to the biosynthetic routes of amino acids, T. cruzi possessestransport systems that allow the active uptake from the extracellular medium; and in the case of polyamines, the uptake is the unique way to obtain these compounds. The TcAAAP protein family is absent in mammals and its members are responsible for amino acid and derivative uptake, thus the TcAAAP permeases are not only interesting and promising therapeutic targets but could also be used to direct the entry of toxic compounds into the parasite.Although there is a treatment available for Chagas disease, its limited efficacy in the chronic stage of the disease, as well as the side effects reported, highlight the urgent need to develop new therapies.Discovery of new drugs is a slow and cost-consuming process, and even during clinical trials the drugs can fail. In this context, drug repositioning is an interesting and recommended strategy by the World Health Organization since costs and time are significantly reduced. In this article, amino acids and polyamines transport and their potential as therapeutic targets will berevised, including examples of synthetic drugs and drug repurposing.