ArticleACS medicinal chemistry letters2016
Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.
Article in ACS medicinal chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed.
- Article
- Identification of Active Compounds against Melanoma Growth by Virtual Screening for Non-Classical Human DHFR Inhibitors.International journal of molecular sciences · 2022Article
- Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.Communications biology · 2022Article
- Hypothesis-Driven, Structure-Based Design in Photopharmacology: The Case of eDHFR Inhibitors.Journal of medicinal chemistry · 2022Article
- The Concept of Folic Acid in Health and Disease.Molecules (Basel, Switzerland) · 2021Review
- 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
- Novel camphor-based pyrimidine derivatives induced cancer cell death through a ROS-mediated mitochondrial apoptosis pathway.RSC advances · 2019Article
- Structure-Guided In Vitro to In Vivo Pharmacokinetic Optimization of Propargyl-Linked Antifolates.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents.Cell chemical biology · 2019Article
- Chemical space of Escherichia coli dihydrofolate reductase inhibitors: New approaches for discovering novel drugs for old bugs.Medicinal research reviews · 2019Review
- In Silico Study Probes Potential Inhibitors of Human Dihydrofolate Reductase for Cancer Therapeutics.Journal of clinical medicine · 2019Article
- Direct Substitution of Arylalkynyl Carbinols Provides Access to Diverse Terminal Acetylene Building Blocks.Organic letters · 2017Article
- MRSA Isolates from United States Hospitals Carry dfrG and dfrK Resistance Genes and Succumb to Propargyl-Linked Antifolates.Cell chemical biology · 2016Article
- Charged Propargyl-Linked Antifolates Reveal Mechanisms of Antifolate Resistance and Inhibit Trimethoprim-Resistant MRSA Strains Possessing Clinically Relevant Mutations.Journal of medicinal chemistry · 2016Article
- Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis.PloS one · 2016Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Although classical, negatively charged antifolates such as methotrexate possess high affinity for the dihydrofolate reductase (DHFR) enzyme, they are unable to penetrate the bacterial cell wall, rendering them poor antibacterial agents. Herein, we report a new class of charged propargyl-linked antifolates that capture some of the key contacts common to the classical antifolates while maintaining the ability to passively diffuse across the bacterial cell wall. Eight synthesized compounds exhibit extraordinary potency against Gram-positive S. aureus with limited toxicity against mammalian cells and good metabolic profile. High resolution crystal structures of two of the compounds reveal extensive interactions between the carboxylate and active site residues through a highly organized water network.
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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.