ArticleAntimicrobial agents and chemotherapy2009
Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
- Peptide Tags for Site-Selective Nonenzymatic Covalent Modification of Proteins.Journal of peptide science : an official publication of the European Peptide Society · 2025Review
- Asymmetric Dearomatization of Phthalazines by Anion-Binding Catalysis.Organic letters · 2023Article
- Inhibitor design to target a unique feature in the folate pocket of Staphylococcus aureus dihydrofolate reductase.European journal of medicinal chemistry · 2020Article
- Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.Journal of the American Chemical Society · 2015Article
- Evaluation of New Dihydrophthalazine-Appended 2,4-Diaminopyrimidines against Bacillus anthracis: Improved Syntheses Using a New Pincer Complex.Molecules (Basel, Switzerland) · 2015Article
- Modified 2,4-diaminopyrimidine-based dihydrofolate reductase inhibitors as potential drug scaffolds against Bacillus anthracis.Bioorganic & medicinal chemistry · 2015Article
- Synthesis and biological evaluation of 2,4-diaminopyrimidine-based antifolate drugs against Bacillus anthracis.Molecules (Basel, Switzerland) · 2014Article
- The structure and competitive substrate inhibition of dihydrofolate reductase from Enterococcus faecalis reveal restrictions to cofactor docking.Biochemistry · 2014Article
- Comparative Study of the Frech Catalyst with Two Conventional Catalysts in the Heck Synthesis of 2,4-Diaminopyrimidine-based Antibiotics.Organic preparations and procedures international · 2013Article
- Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.Biochimica et biophysica acta · 2013Article
- Inhibition of bacterial dihydrofolate reductase by 6-alkyl-2,4-diaminopyrimidines.ChemMedChem · 2012Article
- Synthesis and biological activity of substituted 2,4-diaminopyrimidines that inhibit Bacillus anthracis.European journal of medicinal chemistry · 2012Article
- Classifying compound mechanism of action for linking whole cell phenotypes to molecular targets.Journal of molecular recognition : JMR · 2012Article
- Approaches to Iodinated Derivatives of Vanillin and Isovanillin.Organic preparations and procedures international · 2012Article
- Microwave-assisted Heck Synthesis of Substituted 2,4-Diaminopyrimidine-based Antibiotics.Organic preparations and procedures international · 2012Article
- Antifolate agents: a patent review (2006 - 2010).Expert opinion on therapeutic patents · 2011Review
- New developments in vaccines, inhibitors of anthrax toxins, and antibiotic therapeutics for Bacillus anthracis.Current medicinal chemistry · 2011Review
- Inhibition of antibiotic-resistant Staphylococcus aureus by the broad-spectrum dihydrofolate reductase inhibitor RAB1.Antimicrobial agents and chemotherapy · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacillus anthracis possesses an innate resistance to the antibiotic trimethoprim due to poor binding to dihydrofolate reductase (DHFR); currently, there are no commercial antibacterials that target this enzyme in B. anthracis. We have previously reported a series of dihydrophthalazine-based trimethoprim derivatives that are inhibitors for this target. In the present work, we have synthesized one compound (RAB1) displaying favorable 50% inhibitory concentration (54 nM) and MIC (< or =12.8 microg/ml) values. RAB1 was cocrystallized with the B. anthracis DHFR in the space group P2(1)2(1)2(1), and X-ray diffraction data were collected to a 2.3-A resolution. Binding of RAB1 causes a conformational change of the side chain of Arg58 and Met37 to accommodate the dihydrophthalazine moiety. Unlike the natural substrate or trimethoprim, the dihydrophthalazine group provides a large hydrophobic anchor that embeds within the DHFR active site and accounts for its selective inhibitory activity against B. anthracis.
Indexed as
Identifiers
What OpenQuestion holds
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.