Examination of multiple Trypanosoma cruzi targets in a new drug discovery approach for Chagas disease
Keywords: 
Trypanosoma cruzi
Triosephosphate isomerase
Sterol 14α-demethylase
CYP51
Dihydroorotate dehydrogenase
Cruzain
Trypanothione reductase
Superoxide dismutase
Pteridine reductase
Dihydrofolate reductase
Thymidylate synthase
Issue Date: 
2022
Publisher: 
Elsevier
ISSN: 
0968-0896
Note: 
This is an open access article under the CC BY-NC-ND license
Citation: 
Beltrán-Hortelano, I. (Iván); Alcolea-Devesa, V. (Verónica); Font, M. (María); et al. "Examination of multiple trypanosoma cruzi targets in a new drug discovery approach for chagas disease". Bioorganic & Medicinal Chemistry. (58), 2022, 116577
Abstract
Chagas disease (CD) is a centenarian neglected parasitosis caused by the protozoan Trypanosoma cruzi (T. cruzi). Despite the continuous efforts of many organizations and institutions, CD is still an important human health problem worldwide. A lack of a safe and affordable treatment has led drug discovery programmes to focus, for years, on the search for molecules enabling interference with enzymes that are essential for T. cruzi survival. In this work, the authors want to offer a brief overview of the different validated targets that are involved in diverse parasite pathways: glycolysis, sterol synthesis, the de novo biosynthesis of pyrimidine nucleotides, the degradative processing of peptides and proteins, oxidative stress damage and purine salvage and nucleotide synthesis and metabolism. Their structural aspects, function, active sites, etc. were studied and considered with the aim of defining molecular bases in the search for new effective treatments for CD. This review also compiles, as much as possible, all the inhibitors reported to date against these T. cruzi targets, serving as a reference for future research in this field.

Files in This Item:
Thumbnail
File
1-s2.0-S096808962100585X-main.pdf
Description
Size
14.27 MB
Format
Adobe PDF


Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.