Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 58, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2021.116577
Keywords
Trypanosoma cruzi; Triosephosphate isomerase; CYP51; Dihydroorotate dehydrogenase; Cruzain; Trypanothione reductase; Superoxide dismutase; Pteridine reductase; Dihydrofolate reductase; Thymidylate synthase; Sterol 14 alpha-demethylase
Funding
- Fundacion Caja Navarra
- Obra Social la Caixa
- Fundacion Roviralta
- Grupo Ubesol
- Inversiones Garcilaso de la Vega
- ISTUN Instituto de Salud Tropical of the Universidad de Navarra
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This article provides an overview of validated targets involved in various pathways of the Trypanosoma cruzi parasite and explores the molecular basis for finding new effective treatments for Chagas disease. The review also compiles all reported inhibitors against these targets, serving as a reference for future research in this field.
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.
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