ArticleInternational journal of antimicrobial agents2015
New small-molecule inhibitors of dihydrofolate reductase inhibit Streptococcus mutans.
Article in International journal of antimicrobial agents, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 47 citations in OpenAlex.
- TargetingACS medicinal chemistry letters · 2026Article
- Drug repurposing for glucosyltransferase inhibition for targeted oral biofilm disruption.NPJ biofilms and microbiomes · 2026Article
- The structure ofInfection and immunity · 2026Article
- Advances and challenges in drug design against dental caries: Application ofJournal of pharmaceutical analysis · 2025Review
- Molecular insights into antibiofilm inhibitors of Streptococcus mutans glucosyltransferases through in silico approaches.Scientific reports · 2025Article
- Computational-aided drug design strategies for drug discovery and development against oral diseases.Frontiers in pharmacology · 2025Review
- Polymer vesicles for the delivery of inhibitors of cariogenic biofilm.Dental materials : official publication of the Academy of Dental Materials · 2024Article
- The role of dsRNA A-to-I editing catalyzed by ADAR family enzymes in the pathogeneses.RNA biology · 2024Review
- Article
- Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity ofJournal of medicinal chemistry · 2023Article
- [Materials for Selective Inhibition ofSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- Thymol Increases Sensitivity of Clinical Col-R Gram-Negative Bacteria to Colistin.Microbiology spectrum · 2022Article
- Expert consensus on early childhood caries management.International journal of oral science · 2022Review
- Regulatory Effect of Irresistin-16 on Competitive Dual-Species Biofilms Composed ofPathogens (Basel, Switzerland) · 2022Article
- Diaryl Urea Derivative Molecule Inhibits CariogenicFrontiers in cellular and infection microbiology · 2022Article
- Novel antimicrobial agents targeting theFrontiers in cellular and infection microbiology · 2022Review
- The Application of Small Molecules to the Control of Typical Species Associated With Oral Infectious Diseases.Frontiers in cellular and infection microbiology · 2022Review
- Small Molecule Compounds, A Novel Strategy againstPathogens (Basel, Switzerland) · 2021Review
- Article
- Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors.The Journal of antibiotics · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Streptococcus mutans is a major aetiological agent of dental caries. Formation of biofilms is a key virulence factor of S. mutans. Drugs that inhibit S. mutans biofilms may have therapeutic potential. Dihydrofolate reductase (DHFR) plays a critical role in regulating the metabolism of folate. DHFR inhibitors are thus potent drugs and have been explored as anticancer and antimicrobial agents. In this study, a library of analogues based on a DHFR inhibitor, trimetrexate (TMQ), an FDA-approved drug, was screened and three new analogues that selectively inhibited S. mutans were identified. The most potent inhibitor had a 50% inhibitory concentration (IC50) of 454.0±10.2nM for the biofilm and 8.7±1.9nM for DHFR of S. mutans. In contrast, the IC50 of this compound for human DHFR was ca. 1000nM, a >100-fold decrease in its potency, demonstrating the high selectivity of the analogue. An analogue that exhibited the least potency for the S. mutans biofilm also had the lowest activity towards inhibiting S. mutans DHFR, further indicating that inhibition of biofilms is related to reduced DHFR activity. These data, along with docking of the most potent analogue to the modelled DHFR structure, suggested that the TMQ analogues indeed selectively inhibited S. mutans through targeting DHFR. These potent and selective small molecules are thus promising lead compounds to develop new effective therapeutics to prevent and treat dental caries.
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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.