ArticleChemistry & biology2008
Structure-guided development of efficacious antifungal agents targeting Candida glabrata dihydrofolate reductase.
Article in Chemistry & biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 44 citations in OpenAlex.
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- Crystal structure of dihydrofolate reductase from the emerging pathogenic fungus Candida auris.Acta crystallographica. Section D, Structural biology · 2023Article
- Targeting DNA Topoisomerase II in Antifungal Chemotherapy.Molecules (Basel, Switzerland) · 2022Review
- QSAR and Molecular Docking Studies of Pyrimidine-Coumarin-Triazole Conjugates as Prospective Anti-Breast Cancer Agents.Molecules (Basel, Switzerland) · 2022Article
- Dihydrofolate Reductase Is a Valid Target for Antifungal Development in the Human PathogenmSphere · 2020Article
- 'Acridines' as New Horizons in Antifungal Treatment.Molecules (Basel, Switzerland) · 2020Review
- Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.The Journal of antibiotics · 2020Review
- Reverse Chemical Genetics: Comprehensive Fitness Profiling Reveals the Spectrum of Drug Target Interactions.PLoS genetics · 2016Article
- 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
- 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
- Crystal structures of Candida albicans dihydrofolate reductase bound to propargyl-linked antifolates reveal the flexibility of active site loop residues critical for ligand potency and selectivity.Chemical biology & drug design · 2011Article
- Antifolate agents: a patent review (2006 - 2010).Expert opinion on therapeutic patents · 2011Review
- 2,4-Diamino-5-(2'-arylpropargyl)pyrimidine derivatives as new nonclassical antifolates for human dihydrofolate reductase inhibition.Journal of molecular graphics & modelling · 2011Article
- Towards the understanding of resistance mechanisms in clinically isolated trimethoprim-resistant, methicillin-resistant Staphylococcus aureus dihydrofolate reductase.Journal of structural biology · 2010Article
- 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Candida glabrata is a lethal fungal pathogen resistant to many antifungal agents and has emerged as a critical target for drug discovery. Over the past several years, we have been developing a class of propargyl-linked antifolates as antimicrobials and hypothesized that these compounds could be effective inhibitors of dihydrofolate reductase (DHFR) from C. glabrata. We initially screened a small collection of these inhibitors and found modest levels of potency. Subsequently, we determined the crystal structure of C. glabrata DHFR bound to a representative inhibitor with data to 1.6 A resolution. Using this structure, we designed and synthesized second-generation inhibitors. These inhibitors bind the C. glabrata DHFR enzyme with subnanomolar potency, display greater than 2000-fold levels of selectivity over the human enzyme, and inhibit the growth of C. glabrata at levels observed with clinically employed therapeutics.
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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.