ArticlePloS one2012
Toward new therapeutics for skin and soft tissue infections: propargyl-linked antifolates are potent inhibitors of MRSA and Streptococcus pyogenes.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
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Who cites it
21 citing papers in PubMed.
- Promising Antifungal Molecules against Mucormycosis Agents Identified from Pandemic Response BoxJournal of fungi (Basel, Switzerland) · 2023Article
- Structure-guided functional studies of plasmid-encoded dihydrofolate reductases reveal a common mechanism of trimethoprim resistance in Gram-negative pathogens.Communications biology · 2022Article
- Berkeleylactones and a Citreohybriddione Analogue fromJournal of natural products · 2021Article
- Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.The Journal of antibiotics · 2020Review
- Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications.International journal of molecular sciences · 2019Review
- The Berkeleylactones, Antibiotic Macrolides from Fungal Coculture.Journal of natural products · 2017Article
- Direct Substitution of Arylalkynyl Carbinols Provides Access to Diverse Terminal Acetylene Building Blocks.Organic letters · 2017Article
- Charged Nonclassical Antifolates with Activity Against Gram-Positive and Gram-Negative Pathogens.ACS medicinal chemistry letters · 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
- Crystal Structures of Trimethoprim-Resistant DfrA1 Rationalize Potent Inhibition by Propargyl-Linked Antifolates.ACS infectious diseases · 2016Article
- Propargyl-Linked Antifolates Are Potent Inhibitors of Drug-Sensitive and Drug-Resistant Mycobacterium tuberculosis.PloS one · 2016Article
- Nonracemic Antifolates Stereoselectively Recruit Alternate Cofactors and Overcome Resistance in S. aureus.Journal of the American Chemical Society · 2015Article
- Protein design algorithms predict viable resistance to an experimental antifolate.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- 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
- Blue light eliminates community-acquired methicillin-resistant Staphylococcus aureus in infected mouse skin abrasions.Photomedicine and laser surgery · 2013Article
- 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
- Exploring the chemical space around 8-mercaptoguanine as a route to new inhibitors of the folate biosynthesis enzyme HPPK.PloS one · 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
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Hospital- and community-acquired, complicated skin and soft tissue infections, often attributed to Staphylococcus aureus and Streptococcus pyogenes, present a significant health burden that is associated with increased health care costs and mortality. As these two species are difficult to discern on diagnosis and are associated with differential profiles of drug resistance, the development of an efficacious antibacterial agent that targets both organisms is a high priority. Herein we describe a structure-based drug development effort that has produced highly potent inhibitors of dihydrofolate reductase from both species. Optimized propargyl-linked antifolates containing a key pyridyl substituent display antibacterial activity against both methicillin-resistant S. aureus and S. pyogenes at MIC values below 0.1 µg/mL and minimal cytotoxicity against mammalian cells. Further evaluation against a panel of clinical isolates shows good efficacy against a range of important phenotypes such as hospital- and community-acquired strains as well as strains resistant to vancomycin.
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