The protozoans Leishmania and Trypanosoma, belonging to the same Trypanosomatidae family, are the causative agents of Leishmaniasis, Chagas disease, and human African trypanosomiasis. Overall, these infections affect millions of people worldwide, posing a serious health issue as well as socio-economical concern. Current treatments are inadequate, mainly due to poor efficacy, toxicity, and emerging resistance; therefore, there is an urgent need for new drugs. Among several molecular targets proposed, trypanothione reductase (TR) is of particular interest for its critical role in controlling the parasite’s redox homeostasis and several classes of active compounds that inhibit TR have been proposed so far. This review provides a comprehensive overview of TR’s structural characterization. In particular, we discuss all the structural features of TR relevant for drug discovery, with a focus on the recent advances made in the understanding of inhibitor binding. The reported cases show how, on the basis of the detailed structural information provided by the crystallographic analysis, it is possible to rationally modify molecular scaffolds to improve their properties.

Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases / Battista, T.; Colotti, G.; Ilari, A.; Fiorillo, A.. - In: MOLECULES. - ISSN 1420-3049. - 25:8(2020). [10.3390/molecules25081924]

Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases

Battista T.;Colotti G.;Ilari A.;Fiorillo A.
2020

Abstract

The protozoans Leishmania and Trypanosoma, belonging to the same Trypanosomatidae family, are the causative agents of Leishmaniasis, Chagas disease, and human African trypanosomiasis. Overall, these infections affect millions of people worldwide, posing a serious health issue as well as socio-economical concern. Current treatments are inadequate, mainly due to poor efficacy, toxicity, and emerging resistance; therefore, there is an urgent need for new drugs. Among several molecular targets proposed, trypanothione reductase (TR) is of particular interest for its critical role in controlling the parasite’s redox homeostasis and several classes of active compounds that inhibit TR have been proposed so far. This review provides a comprehensive overview of TR’s structural characterization. In particular, we discuss all the structural features of TR relevant for drug discovery, with a focus on the recent advances made in the understanding of inhibitor binding. The reported cases show how, on the basis of the detailed structural information provided by the crystallographic analysis, it is possible to rationally modify molecular scaffolds to improve their properties.
2020
Protein crystallography; Rational drug discovery; Structure-based drug design; Trypanosomatid infection; Trypanothione reductase
01 Pubblicazione su rivista::01a Articolo in rivista
Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases / Battista, T.; Colotti, G.; Ilari, A.; Fiorillo, A.. - In: MOLECULES. - ISSN 1420-3049. - 25:8(2020). [10.3390/molecules25081924]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1467188
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