Structural insights into the enzymes of the trypanothione pathway: targets for antileishmaniasis drugs. (October 2013)

• Record Type: Journal Article
• Authors: Colotti, Gianni; Baiocco, Paola; Fiorillo, Annarita; Boffi, Alberto; Poser, Elena; Chiaro, Francesco Di; Ilari, Andrea
• Is Part Of: Future medicinal chemistry. Volume 5:Number 15(2013)
• Page Start: 1861
• Page End: 1875
• Publication Date: 2013-10
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc.13.146
• Languages: English
• ISSNs: 1756-8919

Abstract

Leishmaniasis is a neglected disease that kills 60, 000 people worldwide, and which is caused by the protozoa Leishmania . The enzymes of the trypanothione pathway: trypanothione synthetase-amidase, trypanothione reductase (TR) and tryparedoxin-dependent peroxidase are absent in human hosts, and are essential for parasite survival and druggable. The most promising target is trypanothione synthetase-amidase, which has been also chemically validated. However, the structural data presented in this review show that TR also should be considered as a good target. Indeed, it is strongly inhibited by silver- and gold-containing compounds, which are active against Leishmania parasites and can be used for the development of novel antileishmanial agents. Moreover, TR trypanothione-binding site is not featureless but contains a sub-pocket where inhibitors bind, potentially useful for the design of new lead compounds.