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

SAYE, MELISA; REIGADA, CHANTAL; GAUNA, LUCRECIA; VALERA-VERA, EDWARD; PEREIRA, CA; MIRANDA, MARIANA

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 Trypanosoma20 cruzi, like protein synthesis, stress resistance, life cycle progression, infection establishment21 and redox balance, among others. In addition to the biosynthetic routes of amino acids, T.22 cruzi possesses transport systems that allow the active uptake from the extracellular medium;23 and in the case of polyamines, the uptake is the unique way to obtain these compounds. The24 TcAAAP protein family is absent in mammals and its members are responsible for amino25 acid and derivative uptake, thus the TcAAAP permeases are not only interesting and26 promising therapeutic targets but also could be used to direct the entry of toxic compounds27 into the parasite.28 Although there is a treatment available for Chagas disease, its limited efficacy in the chronic29 stage of the disease, as well as the side effects reported, highlight the urgent need to develop30 new therapies. Discovery of new drugs is a slow and money-consuming process, and even31 during clinical trials the drugs can fail. In this context, drug repositioning is an interesting and32 recommended strategy by the World Health Organization since costs and time are33 significantly reduced.34 In this article, amino acids and polyamines transport and its potential as therapeutic targets35 will be revised, including examples of synthetic drugs and drug repurposing.