ArticleAntimicrobial agents and chemotherapy2015
Novel riboswitch-binding flavin analog that protects mice against Clostridium difficile infection without inhibiting cecal flora.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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Who cites it
58 citing papers in PubMed, 100 citations in OpenAlex.
- Designing small molecules targeting a cryptic RNA binding site through base displacement.Nature chemical biology · 2026Article
- Effect of riboflavin and roseoflavin, a structural analogue of riboflavin, on the growth of selected microbial isolates from human saliva using a riboflavin-free cultivation medium.Folia microbiologica · 2025Article
- Machine Learning-Augmented Molecular Dynamics Simulations (MD) Reveal Insights Into the Disconnect Between Affinity and Activation of ZTP Riboswitch Ligands.Angewandte Chemie (International ed. in English) · 2025Article
- Rational development of FMN-based orthogonal riboswitch that functions in response to specific non-cognate ligand.Nature communications · 2025Article
- Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.ACS chemical biology · 2025Article
- Flavin and deazaflavin biosynthesis in mycobacteria: relevance to physiology, implications for drug discovery, MR-1 antigenicity, and vaccine development.Frontiers in immunology · 2025Review
- Two riboswitch classes that share a common ligand-binding fold show major differences in the ability to accommodate mutations.Nucleic acids research · 2024Article
- TheRNA (New York, N.Y.) · 2024Article
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- Identification of RNA structures and their roles in RNA functions.Nature reviews. Molecular cell biology · 2024Review
- The current riboswitch landscape inMicrobiology (Reading, England) · 2024Review
- A sensitive and scalable fluorescence anisotropy single stranded RNA targeting approach for monitoring riboswitch conformational states.Nucleic acids research · 2024Article
- Fluorescent Ligand Equilibrium Displacement: A High-Throughput Method for Identification of FMN Riboswitch-Binding Small Molecules.International journal of molecular sciences · 2024Article
- Ribocentre-switch: a database of riboswitches.Nucleic acids research · 2024Article
- Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational Antibacterial Drug Development.Antibiotics (Basel, Switzerland) · 2023Review
- Efficient production of bacterial antibiotics aminoriboflavin and roseoflavin in eukaryotic microorganisms, yeasts.Microbial cell factories · 2023Article
- Targeting Riboswitches with Beta-Axial-Substituted Cobalamins.ACS chemical biology · 2023Article
- Discovering riboswitches: the past and the future.Trends in biochemical sciences · 2023Review
- Characterizing RNA-binding ligands on structures, chemical information, binding affinity and drug-likeness.RNA biology · 2023Article
- X-Ray Crystallography to Study Conformational Changes in a TPP Riboswitch.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Novel mechanisms of action and new chemical scaffolds are needed to rejuvenate antibacterial drug discovery, and riboswitch regulators of bacterial gene expression are a promising class of targets for the discovery of new leads. Herein, we report the characterization of 5-(3-(4-fluorophenyl)butyl)-7,8-dimethylpyrido[3,4-b]quinoxaline-1,3(2H,5H)-dione (5FDQD)-an analog of riboflavin that was designed to bind riboswitches that naturally recognize the essential coenzyme flavin mononucleotide (FMN) and regulate FMN and riboflavin homeostasis. In vitro, 5FDQD and FMN bind to and trigger the function of an FMN riboswitch with equipotent activity. MIC and time-kill studies demonstrated that 5FDQD has potent and rapidly bactericidal activity against Clostridium difficile. In C57BL/6 mice, 5FDQD completely prevented the onset of lethal antibiotic-induced C. difficile infection (CDI). Against a panel of bacteria representative of healthy bowel flora, the antibacterial selectivity of 5FDQD was superior to currently marketed CDI therapeutics, with very little activity against representative strains from the Bacteroides, Lactobacillus, Bifidobacterium, Actinomyces, and Prevotella genera. Accordingly, a single oral dose of 5FDQD caused less alteration of culturable cecal flora in mice than the comparators. Collectively, these data suggest that 5FDQD or closely related analogs could potentially provide a high rate of CDI cure with a low likelihood of infection recurrence. Future studies will seek to assess the role of FMN riboswitch binding to the mechanism of 5FDQD antibacterial action. In aggregate, our results indicate that riboswitch-binding antibacterial compounds can be discovered and optimized to exhibit activity profiles that merit preclinical and clinical development as potential antibacterial therapeutic agents.
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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.