ArticleInfectious diseases of poverty2015
High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis.
Article in Infectious diseases of poverty, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Screening Novel Furoxan Derivatives as Potential Inhibitors Targeting Thioredoxin Glutathione Reductase ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Molluscicidal and Schistosomicidal Activities of 2-(1Pharmaceuticals (Basel, Switzerland) · 2025Article
- The "Doorstop Pocket" In Thioredoxin Reductases─An Unexpected Druggable Regulator of the Catalytic Machinery.Journal of medicinal chemistry · 2024Review
- Fragment library screening by X-ray crystallography and binding site analysis on thioredoxin glutathione reductase of Schistosoma mansoni.Scientific reports · 2024Article
- Proteomics Studies Suggest That Nitric Oxide Donor Furoxans Inhibit In Vitro Vascular Smooth Muscle Cell Proliferation by Nitric Oxide-Independent Mechanisms.Molecules (Basel, Switzerland) · 2023Article
- First In Silico Screening of Insect Molecules for Identification of Novel Anti-Parasitic Compounds.Pharmaceuticals (Basel, Switzerland) · 2022Article
- A Machine Learning Strategy for Drug Discovery Identifies Anti-Schistosomal Small Molecules.ACS infectious diseases · 2021Article
- Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence.Frontiers in immunology · 2021Review
- Identification of annotated bioactive molecules that impair motility of the blood fluke Schistosoma mansoni.International journal for parasitology. Drugs and drug resistance · 2020Article
- Chemotherapy for human schistosomiasis: how far have we come? What's new? Where do we go from here?RSC medicinal chemistry · 2020Review
- Characterization of Lead Compounds Targeting the Selenoprotein Thioredoxin Glutathione Reductase for Treatment of Schistosomiasis.ACS infectious diseases · 2020Article
- Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death.Science advances · 2020Article
- Ectopic suicide inhibition of thioredoxin glutathione reductase.Free radical biology & medicine · 2020Article
- Antiplasmodial Activity of Nitroaromatic Compounds: Correlation with Their Reduction Potential and Inhibitory Action onMolecules (Basel, Switzerland) · 2019Article
- Pharmacokinetics and pharmacodynamics of nitric oxide mimetic agents.Nitric oxide : biology and chemistry · 2019Review
- A novel cell-free method to culture Schistosoma mansoni from cercariae to juvenile worm stages for in vitro drug testing.PLoS neglected tropical diseases · 2019Article
- High Throughput and Computational Repurposing for Neglected Diseases.Pharmaceutical research · 2018Review
- Innovation in neglected tropical disease drug discovery and development.Infectious diseases of poverty · 2018Review
- The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites.Molecules (Basel, Switzerland) · 2017Review
- CancerResource--updated database of cancer-relevant proteins, mutations and interacting drugs.Nucleic acids research · 2016Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundSchistosomiasis, a parasitic disease also known as bilharzia and snail fever, is caused by different species of flatworms, such as Schistosoma mansoni (S. mansoni). Thioredoxin glutathione reductase (TGR) from S. mansoni (SmTGR) is a well-characterized drug target for schistosomiasis, yet no anti-SmTGR compounds have reached clinical trials, suggesting that therapeutic development against schistosomiasis might benefit from additional scaffolds targeting this enzyme.
methodsA high-throughput screening (HTS) assay in vitro against SmTGR was developed and applied to a diverse compound library. SmTGR activity was quantified with ThioGlo®, a reagent that fluoresces upon binding to the free sulfhydryl groups of the reaction product GSH (reduced glutathione).
resultsWe implemented an HTS effort against 59,360 synthetic compounds. In the primary screening, initial hits (928 or 1.56 %) showing greater than 90 % inhibition on SmTGR activity at a final concentration of 10 μM for each compound were identified. Further tests were carried out to confirm the effects of these hits and to explore the concentration-dependent response characteristics. As a result, 74 of them (0.12 %) representing 17 chemical scaffolds were confirmed and showed a great concentration-dependent inhibitory trend against SmTGR, including structures previously shown to be lethal to schistosomal growth. Of these, two scaffolds displayed a limited structure-activity relationship. When tested in cultured larvae, 39 compounds had cidal activity in 48 h, and five of them killed larvae completely at 3.125 μM. Of these, three compounds also killed adult worms ex vivo at concentrations between 5 μM and 10 μM.
conclusionThese confirmed hits may serve as starting points for the development of novel therapeutics to combat schistosomiasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.