ArticleJournal of medicinal chemistry2010
Structure-based design of pteridine reductase inhibitors targeting African sleeping sickness and the leishmaniases.
Article in Journal of medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The trial behind it
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Who cites it
35 citing papers in PubMed, 86 citations in OpenAlex.
- Design of 2-Aminobenzothiazole Derivatives Targeting Trypanosomatid PTR1 by a Multidisciplinary Fragment Hybridization Approach.Journal of medicinal chemistry · 2025Article
- Designing Antitrypanosomal and Antileishmanial BODIPY Derivatives: A Computational and In Vitro Assessment.Molecules (Basel, Switzerland) · 2024Article
- The allure of targets for novel drugs.RSC medicinal chemistry · 2024Review
- Polyamine Metabolism for Drug Intervention in Trypanosomatids.Pathogens (Basel, Switzerland) · 2024Review
- Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design.European biophysics journal : EBJ · 2023Review
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1.Nature communications · 2023Article
- Synthesis and Antiprotozoal Activity of Azabicyclo-Nonane Pyrimidine Hybrids.Molecules (Basel, Switzerland) · 2022Article
- Prediction of Antileishmanial Compounds: General Model, Preparation, and Evaluation of 2-Acylpyrrole Derivatives.Journal of chemical information and modeling · 2022Article
- Multitarget, Selective Compound Design Yields Potent Inhibitors of a Kinetoplastid Pteridine Reductase 1.Journal of medicinal chemistry · 2022Article
- Crystal structure of the ternary complex of Leishmania major pteridine reductase 1 with the cofactor NADPActa crystallographica. Section F, Structural biology communications · 2022Article
- Synthesis and Biological Evaluation of Tetrahydropyrimidine and Dihydropyridine Derivatives Against Leishmania Major.Acta parasitologica · 2022Article
- Crystal structures of FolM alternative dihydrofolate reductase 1 from Brucella suis and Brucella canis.Acta crystallographica. Section F, Structural biology communications · 2022Article
- Repurposing the Trypanosomatidic GSK Kinetobox for the Inhibition of Parasitic Pteridine and Dihydrofolate Reductases.Pharmaceuticals (Basel, Switzerland) · 2021Article
- An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases.Molecules (Basel, Switzerland) · 2021Review
- Evidence of Pyrimethamine and Cycloguanil Analogues as Dual Inhibitors ofPharmaceuticals (Basel, Switzerland) · 2021Article
- Novel Soil-Derived Beta-Lactam, Chloramphenicol, Fosfomycin and Trimethoprim Resistance Genes Revealed by Functional Metagenomics.Antibiotics (Basel, Switzerland) · 2021Article
- Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin.Beilstein journal of organic chemistry · 2020Article
- New Conformations of Acylation Adducts of Inhibitors of β-Lactamase from Mycobacterium tuberculosis.Biochemistry · 2019Article
- Identification of Novel Potential Inhibitors of Pteridine Reductase 1 inMolecules (Basel, Switzerland) · 2019Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-species specific properties explained by structural differences between the T. brucei and L. major enzymes. The most potent inhibitors target T. brucei PTR1, and two compounds displayed antiparasite activity against the bloodstream form of the parasite. PTR1 contributes to antifolate drug resistance by providing a molecular bypass of dihydrofolate reductase (DHFR) inhibition. Therefore, combining PTR1 and DHFR inhibitors might improve therapeutic efficacy. We tested two new compounds with known DHFR inhibitors. A synergistic effect was observed for one particular combination highlighting the potential of such an approach for treatment of African sleeping sickness.
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Registered trials
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