Trypanothione as a Target in the Design of Antitrypanosomal and Antileishmanial Agents

K.      Augustyns; K.      Amssoms; A.      Yamani; P.   K.   Rajan; A.      Haemers

doi:10.2174/1381612013397564

Abstract

Trypanothione is the key molecule in the defence mechanism of Trypanosoma and Leishmania against oxidative stress. The uniqueness of trypanothione makes the metabolism of this molecule an attractive target in antitrypanosomal and antileishmanial drug design. It became clear that this antioxidant cascade can be considered as the Achilles heel of these parasites. The following targets and their respective inhibitors will be discussed biosynthesis of trypanothione with glutathionylspermidine synthetase and trypanothione synthetase biosynthesis of glutathione with gama-glutamylcysteine synthetase biosynthesis of spermidine with ornithine decarboxylase trypanothione hydroperoxide metabolism with tryparedoxine peroxidase, tryparedoxine and trypanothione reductase.

Keywords: Trypanothione, Antitrypanosomal, Antileishmanial Agents, oxidative stress, glutathionylspermidine synthetase, trypanothione synthetase, g-glutamylcysteine, spermidine, ornithine, decarboxylase