ArticleChemMedChem2011
Design, synthesis and biological evaluation of novel inhibitors of Trypanosoma brucei pteridine reductase 1.
Article in ChemMedChem, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Design of 2-Aminobenzothiazole Derivatives Targeting Trypanosomatid PTR1 by a Multidisciplinary Fragment Hybridization Approach.Journal of medicinal chemistry · 2025Article
- Comparative metabolism of conjugated and unconjugated pterins in Crithidia, Leishmania and African trypanosomes.PLoS neglected tropical diseases · 2025Article
- Structure and dynamics of pteridine reductase 1: the key phenomena relevant to enzyme function and drug design.European biophysics journal : EBJ · 2023Review
- Multitarget, Selective Compound Design Yields Potent Inhibitors of a Kinetoplastid Pteridine Reductase 1.Journal of medicinal chemistry · 2022Article
- Synthesis and Biological Evaluation of Tetrahydropyrimidine and Dihydropyridine Derivatives Against Leishmania Major.Acta parasitologica · 2022Article
- Leishmanicidal Activity of Betulin Derivatives inMicroorganisms · 2021Article
- Design, Synthesis and Biological Evaluation of Arylpyridin-2-yl Guanidine Derivatives and Cyclic Mimetics as Novel MSK1 Inhibitors. An Application in an Asthma Model.Molecules (Basel, Switzerland) · 2021Article
- Computational approaches for drug discovery against trypanosomatid-caused diseases.Parasitology · 2020Review
- Article
- Development of Chemical Proteomics for the Folateome and Analysis of the Kinetoplastid Folateome.ACS infectious diseases · 2018Article
- Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To InhibitACS omega · 2017Article
- Application of a simple quantum chemical approach to ligand fragment scoring for Trypanosoma brucei pteridine reductase 1 inhibition.Journal of computer-aided molecular design · 2017Article
- The Role of Folate Transport in Antifolate Drug Action in Trypanosoma brucei.The Journal of biological chemistry · 2016Article
- Design, Synthesis and Biological Evaluation of Novel HIF1α Inhibitors.Anticancer research · 2015Article
- Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1.Journal of medicinal chemistry · 2014Article
- Drug discovery for neglected diseases: molecular target-based and phenotypic approaches.Journal of medicinal chemistry · 2013Review
- Article
- 3D-QSAR based pharmacophore modeling and virtual screening for identification of novel pteridine reductase inhibitors.Journal of molecular modeling · 2012Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Genetic studies indicate that the enzyme pteridine reductase 1 (PTR1) is essential for the survival of the protozoan parasite Trypanosoma brucei. Herein, we describe the development and optimisation of a novel series of PTR1 inhibitors, based on benzo[d]imidazol-2-amine derivatives. Data are reported on 33 compounds. This series was initially discovered by a virtual screening campaign (J. Med. Chem., 2009, 52, 4454). The inhibitors adopted an alternative binding mode to those of the natural ligands, biopterin and dihydrobiopterin, and classical inhibitors, such as methotrexate. Using both rational medicinal chemistry and structure-based approaches, we were able to derive compounds with potent activity against T. brucei PTR1 (K(i)(app)=7 nM), which had high selectivity over both human and T. brucei dihydrofolate reductase. Unfortunately, these compounds displayed weak activity against the parasites. Kinetic studies and analysis indicate that the main reason for the lack of cell potency is due to the compounds having insufficient potency against the enzyme, which can be seen from the low K(m) to K(i) ratio (K(m)=25 nM and K(i)=2.3 nM, respectively).
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Registered trials
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.