A fast virtual screening approach to identify structurally diverse inhibitors of trypanothione reductase

Giorgio Maccari; Timo Jaeger; Francesca Moraca; Mariangela Biava; Leopold Flohé; Maurizio Botta

doi:10.1016/j.bmcl.2011.07.036

A fast virtual screening approach to identify structurally diverse inhibitors of trypanothione reductase

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5255-8. doi: 10.1016/j.bmcl.2011.07.036. Epub 2011 Jul 19.

Authors

Giorgio Maccari¹, Timo Jaeger, Francesca Moraca, Mariangela Biava, Leopold Flohé, Maurizio Botta

Affiliation

¹ Università degli Studi di Siena, Via a Moro 2, I-53100 Siena, Italy.

PMID: 21807515
DOI: 10.1016/j.bmcl.2011.07.036

Abstract

Trypanothione reductase (TryR) is one of the favorite targets for those designing drugs for the treatment of Chagas disease. We present the application of a fast virtual screening approach for designing hit compounds active against TryR. Our protocol combines information derived from structurally known inhibitors and from the TryR receptor structure. Five structurally diverse hit compounds active against TryR and holding promise for the treatment of Chagas disease are reported.

MeSH terms

Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
High-Throughput Screening Assays*
Models, Molecular
Molecular Structure
NADH, NADPH Oxidoreductases / antagonists & inhibitors*
NADH, NADPH Oxidoreductases / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Enzyme Inhibitors
NADH, NADPH Oxidoreductases
trypanothione reductase