ArticleThe Journal of biological chemistry2013
Ebsulfur is a benzisothiazolone cytocidal inhibitor targeting the trypanothione reductase of Trypanosoma brucei.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 54 citations in OpenAlex.
- Ebselen restores mitochondrial function through metabolic rewiring in Barth syndrome and related mitochondrial diseases.EMBO molecular medicine · 2026Article
- Selenocyanate-Containing Molecules as Trypanosoma cruzi Inhibitors: Impact of Regioisomerism, Conformational Restriction, and Second-Ring Substitution.ChemMedChem · 2026Article
- Barbituric Acid Derivatives as Covalent Inhibitors ofJournal of medicinal chemistry · 2025Article
- Towards a Holistic Understanding of the Interactions of Redox-Active Proteins.Antioxidants (Basel, Switzerland) · 2024Article
- Covalent Inhibitors for Neglected Diseases: An Exploration of Novel Therapeutic Options.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Facile Synthesis and In Vitro Activity ofPathogens (Basel, Switzerland) · 2021Article
- Ebselen, a new candidate therapeutic against SARS-CoV-2.International journal of surgery (London, England) · 2020Article
- Potential therapeutic use of ebselen for COVID-19 and other respiratory viral infections.Free radical biology & medicine · 2020Review
- Computational approaches for drug discovery against trypanosomatid-caused diseases.Parasitology · 2020Review
- NADPH-dependent and -independent disulfide reductase systems.Free radical biology & medicine · 2018Review
- Diglycosyl diselenides alter redox homeostasis and glucose consumption of infective African trypanosomes.International journal for parasitology. Drugs and drug resistance · 2017Article
- Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery.Antimicrobial agents and chemotherapy · 2017Article
- The establishment of in vitro culture and drug screening systems for a newly isolated strain of Trypanosoma equiperdum.International journal for parasitology. Drugs and drug resistance · 2017Article
- Synergistic antibacterial effect of silver and ebselen against multidrug-resistant Gram-negative bacterial infections.EMBO molecular medicine · 2017Article
- Essential multimeric enzymes in kinetoplastid parasites: A host of potentially druggable protein-protein interactions.PLoS neglected tropical diseases · 2017Article
- Development of ebsulfur analogues as potent antibacterials against methicillin-resistant Staphylococcus aureus.Bioorganic & medicinal chemistry · 2016Article
- Article
- The Oral Antimalarial Drug Tafenoquine Shows Activity against Trypanosoma brucei.Antimicrobial agents and chemotherapy · 2015Article
- Ebselen inhibits hepatitis C virus NS3 helicase binding to nucleic acid and prevents viral replication.ACS chemical biology · 2014Article
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured parasites. The inhibition of TryR by EbS was irreversible and NADPH-dependent. EbS formed a complex with TryR and caused oxidation and inactivation of the enzyme. EbS was more toxic for T. brucei than for Trypanosoma cruzi, probably due to lower levels of TryR and trypanothione in T. brucei. Furthermore, inhibition of TryR produced high intracellular reactive oxygen species. Hydrogen peroxide, known to be constitutively high in T. brucei, enhanced the EbS inhibition of TryR. The elevation of reactive oxygen species production in parasites caused by EbS induced a programmed cell death. Soluble EbS analogues were synthesized and cured T. brucei brucei infection in mice when used together with nifurtimox. Altogether, EbS and EbS analogues disrupt the trypanothione system, hampering the defense against oxidative stress. Thus, EbS is a promising lead for development of drugs against African trypanosomiasis.
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