ArticleJournal of medicinal chemistry2016
Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed, 31 citations in OpenAlex.
- Antioxidant, antibacterial, and molecular docking of methyl ferulate and oleic acid produced by Aspergillus pseudodeflectus AUMC 15761 utilizing wheat bran.Scientific reports · 2024Article
- Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.Communications biology · 2022Article
- Synthesis, Biological Activity and Molecular Docking Studies of Novel Nicotinic Acid Derivatives.International journal of molecular sciences · 2022Article
- Chiral evasion and stereospecific antifolate resistance in Staphylococcus aureus.PLoS computational biology · 2022Article
- Development of antibacterial compounds that constrain evolutionary pathways to resistance.eLife · 2021Article
- Inhibitor design to target a unique feature in the folate pocket of Staphylococcus aureus dihydrofolate reductase.European journal of medicinal chemistry · 2020Article
- Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.The Journal of antibiotics · 2020Review
- Toward Broad Spectrum Dihydrofolate Reductase Inhibitors Targeting Trimethoprim Resistant Enzymes Identified in Clinical Isolates of Methicillin ResistantACS infectious diseases · 2019Article
- Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents.Cell chemical biology · 2019Article
- eModel-BDB: a database of comparative structure models of drug-target interactions from the Binding Database.GigaScience · 2018Article
- MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates.Cell chemical biology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Drug-resistant enzymes must balance catalytic function with inhibitor destabilization to provide a fitness advantage. This sensitive balance, often involving very subtle structural changes, must be achieved through a selection process involving a minimal number of eligible point mutations. As part of a program to design propargyl-linked antifolates (PLAs) against trimethoprim-resistant dihydrofolate reductase (DHFR) from Staphylococcus aureus, we have conducted a thorough study of several clinically observed chromosomal mutations in the enzyme at the cellular, biochemical, and structural levels. Through this work, we have identified a promising lead series that displays significantly greater activity against these mutant enzymes and strains than TMP. The best inhibitors have enzyme inhibition and MIC values near or below that of trimethoprim against wild-type S. aureus. Moreover, these studies employ a series of crystal structures of several mutant enzymes bound to the same inhibitor; analysis of the structures reveals a more detailed molecular understanding of drug resistance in this important enzyme.
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Registered trials
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