ArticlePLoS neglected tropical diseases2008
Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo.
Article in PLoS neglected tropical diseases, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed.
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- Prenyl Transferases Regulate Secretory Protein Sorting and Parasite Morphology inInternational journal of molecular sciences · 2023Article
- Building Programs to Eradicate Toxoplasmosis Part IV: Understanding and Development of Public Health Strategies and Advances "Take a Village".Current pediatrics reports · 2022Review
- Building Programs to Eradicate Toxoplasmosis Part I: Introduction and Overview.Current pediatrics reports · 2022Review
- A Novel Combined DNA Vaccine Encoding Toxoplasma gondii SAG1 and ROP18 Provokes Protective Immunity Against a Lethal Challenge in Mice.Acta parasitologica · 2021Article
- [Toxoplasma gondii-Current drugs and future vaccines against an underestimated protozoan infection].Der Internist · 2021Review
- Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock.Antimicrobial agents and chemotherapy · 2020Article
- Use of Veterinary Vaccines for Livestock as a Strategy to Control Foodborne Parasitic Diseases.Frontiers in cellular and infection microbiology · 2020Review
- Anti-Toxoplasma activity of Sorghum bicolor-derived lipophilic fractions.BMC research notes · 2019Article
- Treatment of toxoplasmosis: Current options and future perspectives.Food and waterborne parasitology · 2019Review
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- Synthesis and biological evaluation of anti-Toxoplasma gondii activity of a novel scaffold of thiazolidinone derivatives.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Drugs in development for toxoplasmosis: advances, challenges, and current status.Drug design, development and therapy · 2017Review
- A Systematic Review ofFrontiers in microbiology · 2017Review
- Discovery of Potent and Selective Leads againstACS medicinal chemistry letters · 2016Article
- Review of Experimental Compounds Demonstrating Anti-Toxoplasma Activity.Antimicrobial agents and chemotherapy · 2016Review
- New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections.Scientific reports · 2016Article
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Authors and funding
15 authors.
Funding
Abstract
background and methodologyToxoplasma gondii causes substantial morbidity, mortality, and costs for healthcare in the developed and developing world. Current medicines are not well tolerated and cause hypersensitivity reactions. The dihydrotriazine JPC-2067-B (4, 6-diamino-1, 2-dihydro-2, 2-dimethyl-1-(3'(2-chloro-, 4-trifluoromethoxyphenoxy)propyloxy)-1, 3, 5-triazine), which inhibits dihydrofolate reductase (DHFR), is highly effective against Plasmodium falciparum, Plasmodium vivax, and apicomplexans related to T. gondii. JPC-2067-B is the primary metabolite of the orally active biguanide JPC-2056 1-(3'-(2-chloro-4-trifluoromethoxyphenyloxy)propyl oxy)- 5-isopropylbiguanide, which is being advanced to clinical trials for malaria. Efficacy of the prodrug JPC-2056 and the active metabolite JPC-2067-B against T. gondii and T. gondii DHFR as well as toxicity toward mammalian cells were tested. PRINCIPAL FINDINGS AND
conclusionsHerein, we found that JPC-2067-B is highly effective against T. gondii. We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM), inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and the orally administered pro-drug (JPC-2056) are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed. We found that the three main parasite clonal types and isolates from South and Central America, the United States, Canada, China, and Sri Lanka have the same amino acid sequences preserving key binding sites for the triazine. SIGNIFICANCE: JPC-2056/JPC-2067-B have potential to be more effective and possibly less toxic treatments for toxoplasmosis than currently available medicines.
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