ArticleInternational journal for parasitology. Drugs and drug resistance2013
Exploring the mode of action of ebselen in Trypanosoma brucei hexokinase inhibition.
Article in International journal for parasitology. Drugs and drug resistance, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Comparative Analysis of the Interaction of Silver Nanoparticles with Hexokinase fromInternational journal of nanomedicine · 2023Article
- Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Ebselen and Analogues: Pharmacological Properties and Synthetic Strategies for Their Preparation.Molecules (Basel, Switzerland) · 2021Review
- Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- The Action of the Hexokinase Inhibitor 2-deoxy-d-glucose on Cryptosporidium parvum and the Discovery of Activities against the Parasite Hexokinase from Marketed Drugs.The Journal of eukaryotic microbiology · 2019Article
- Discovery of ebselen as an inhibitor of Cryptosporidium parvum glucose-6-phosphate isomerase (CpGPI) by high-throughput screening of existing drugs.International journal for parasitology. Drugs and drug resistance · 2018Article
- Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes.International journal for parasitology. Drugs and drug resistance · 2017Article
- A targeted delivery strategy for the development of potent trypanocides.Chemical communications (Cambridge, England) · 2017Article
- Evaluation of substituted ebselen derivatives as potential trypanocidal agents.Bioorganic & medicinal chemistry letters · 2017Article
- Advanced enzymology, expression profile and immune response of Clonorchis sinensis hexokinase show its application potential for prevention and control of clonorchiasis.PLoS neglected tropical diseases · 2015Article
- Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication.ACS chemical biology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Glycolysis is essential to Trypanosoma brucei, the causative agent of African sleeping sickness, suggesting enzymes in the pathway could be targets for drug development. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one, EbSe) was identified in a screen as a potent inhibitor of T. brucei hexokinase 1 (TbHK1), the first enzyme in the pathway. EbSe has a history of promiscuity as an enzyme inhibitor, inactivating proteins through seleno-sulfide conjugation with Cys residues. Indeed, dilution of TbHK1 and inhibitor following incubation did not temper inhibition suggesting conjugate formation. Using mass spectrometry to analyze EbSe-based modifications revealed that two Cys residues (C327 and C369) were oxidized after treatment. Site-directed mutagenesis of C327 led to enzyme inactivation indicating that C327 was essential for catalysis. C369 was not essential, suggesting that EbSe inhibition of TbHK1 was the consequence of modification of C327 via thiol oxidation. Additionally, neither EbSe treatment nor mutation of the nine TbHK1 Cys residues appreciably altered enzyme quaternary structure.
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