ArticleAntimicrobial agents and chemotherapy2007
In vitro efficacy of new antifolates against trimethoprim-resistant Bacillus anthracis.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Antiproliferative Activity of (-)-Isopulegol-based 1,3-Oxazine, 1,3-Thiazine and 2,4-Diaminopyrimidine Derivatives.ChemistryOpen · 2022Article
- Genome-Scale Metabolic Modeling for Unraveling Molecular Mechanisms of High Threat Pathogens.Frontiers in cell and developmental biology · 2020Review
- 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
- Metabolic network analysis-based identification of antimicrobial drug targets in category A bioterrorism agents.PloS one · 2014Article
- Structure-activity relationship for enantiomers of potent inhibitors of B. anthracis dihydrofolate reductase.Biochimica et biophysica acta · 2013Article
- 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
- 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
- High-throughput screening of a diversity collection using biodefense category A and B priority pathogens.Journal of biomolecular screening · 2012Article
- Classifying compound mechanism of action for linking whole cell phenotypes to molecular targets.Journal of molecular recognition : JMR · 2012Article
- Microwave-assisted Heck Synthesis of Substituted 2,4-Diaminopyrimidine-based Antibiotics.Organic preparations and procedures international · 2012Article
- New developments in vaccines, inhibitors of anthrax toxins, and antibiotic therapeutics for Bacillus anthracis.Current medicinal chemistry · 2011Review
- Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure−activity relationships.Journal of medicinal chemistry · 2010Article
- Inhibition of antibiotic-resistant Staphylococcus aureus by the broad-spectrum dihydrofolate reductase inhibitor RAB1.Antimicrobial agents and chemotherapy · 2010Article
- Crystal structure of Bacillus anthracis dihydrofolate reductase with the dihydrophthalazine-based trimethoprim derivative RAB1 provides a structural explanation of potency and selectivity.Antimicrobial agents and chemotherapy · 2009Article
- X-ray structure of the ternary MTX.NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design.Journal of structural biology · 2009Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Bacillus anthracis is innately resistant to trimethoprim (TMP), a synthetic antifolate that selectively inhibits several bacterial dihydrofolate reductases (DHFRs) but not human DHFR. Previously, we were able to confirm that TMP resistance in B. anthracis (MIC > 2,048 microg/ml) is due to the lack of selectivity of TMP for the B. anthracis DHFR (E. W. Barrow, P. C. Bourne, and W. W. Barrow, Antimicrob. Agents Chemother. 48:4643-4649, 2004). In this investigation, 24 2,4-diaminopyrimidine derivatives, representing a class of compounds with dihydrophthalazine side chains, were screened for their in vitro effects on B. anthracis Sterne and their selectivities for the B. anthracis DHFR. MICs were obtained by a colorimetric (Alamar blue) broth microdilution assay. Purified human recombinant DHFR (rDHFR) and B. anthracis rDHFR were used in a validated enzyme assay to determine the 50% inhibitory concentrations (IC(50)s) and the selectivity ratios of the derivatives. The MICs ranged from 12.8 to 128 microg/ml for all but nine compounds, for which the MICs were > or =128 microg/ml. The IC(50) values for B. anthracis rDHFR ranged from 46 to 600 nM, whereas the IC(50) values for human rDHFR were >16,000 nM. This is the first report on the in vitro inhibitory actions of this class of antifolates against TMP-resistant B. anthracis isolates. The selective inhibition of B. anthracis rDHFR and the in vitro activity against B. anthracis demonstrate that members of this class of compounds have the potential to be developed into clinically important therapeutic choices for the treatment of infections caused by TMP-resistant bacteria, such as B. anthracis.
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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.