ArticleJournal of medicinal chemistry2008
Structure-based approach to the development of potent and selective inhibitors of dihydrofolate reductase from cryptosporidium.
Article in Journal of medicinal chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Crystal structure of dihydrofolate reductase from the filarial nematode W. bancrofti in complex with NADPH and folate.PLoS neglected tropical diseases · 2023Article
- Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry · 2019Article
- Direct Substitution of Arylalkynyl Carbinols Provides Access to Diverse Terminal Acetylene Building Blocks.Organic letters · 2017Article
- Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.Journal of the American Chemical Society · 2015Article
- Three-dimensional structures in the design of therapeutics targeting parasitic protozoa: reflections on the past, present and future.Acta crystallographica. Section F, Structural biology communications · 2015Review
- Crystal structures of Klebsiella pneumoniae dihydrofolate reductase bound to propargyl-linked antifolates reveal features for potency and selectivity.Antimicrobial agents and chemotherapy · 2014Article
- Propargyl-linked antifolates are dual inhibitors of Candida albicans and Candida glabrata.Journal of medicinal chemistry · 2014Article
- Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.Biochemistry · 2013Article
- Substituted pyrrolo[2,3-d]pyrimidines as Cryptosporidium hominis thymidylate synthase inhibitors.Bioorganic & medicinal chemistry letters · 2013Article
- Exploring novel strategies for AIDS protozoal pathogens: α-helix mimetics targeting a key allosteric protein-protein interaction inMedChemComm · 2013Article
- Structural analysis of the active sites of dihydrofolate reductase from two species of Candida uncovers ligand-induced conformational changes shared among species.Bioorganic & medicinal chemistry letters · 2013Article
- Acetylenic linkers in lead compounds: a study of the stability of the propargyl-linked antifolates.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
- Prospective screening of novel antibacterial inhibitors of dihydrofolate reductase for mutational resistance.Antimicrobial agents and chemotherapy · 2012Article
- Article
- 2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition.Journal of molecular graphics & modelling · 2011Article
- Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure−activity relationships.Journal of medicinal chemistry · 2010Article
- Towards the understanding of resistance mechanisms in clinically isolated trimethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase.Journal of structural biology · 2010Article
- Cryptosporidium: genomic and biochemical features.Experimental parasitology · 2010Review
- Scoring ensembles of docked protein:ligand interactions for virtual lead optimization.Journal of chemical information and modeling · 2009Article
- In vitro biological activity and structural analysis of 2,4-diamino-5-(2'-arylpropargyl)pyrimidine inhibitors of Candida albicans.Bioorganic & medicinal chemistry · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cryptosporidiosis is an emerging infectious disease that can be life-threatening in an immune-compromised individual and causes gastrointestinal distress lasting up to 2 weeks in an immune-competent individual. There are few therapeutics available for effectively treating this disease. We have been exploring dihydrofolate reductase (DHFR) as a potential target in Cryptosporidium. On the basis of the structure of the DHFR enzyme from C. hominis, we have developed a novel scaffold that led to the discovery of potent (38 nM) and efficient inhibitors of this enzyme. Recently, we have advanced these inhibitors to the next stage of development. Using the structures of both the protozoal and human enzymes, we have developed inhibitors with nanomolar potency (1.1 nM) against the pathogenic enzyme and high levels (1273-fold) of selectivity over the human enzyme.
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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.