ArticleAntimicrobial agents and chemotherapy2012
Pyrrolamide DNA gyrase inhibitors: fragment-based nuclear magnetic resonance screening to identify antibacterial agents.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 134 citations in OpenAlex.
- Antibacterial and Antibiofilm Activity of a Chemically Characterized Cinnamomum verum Bark Methanolic Extract Against Multidrug-Resistant Bacteria: Preliminary Antibiotic-Interaction Screening and Exploratory Molecular Docking.Chemistry & biodiversity · 2026Article
- Synthesis, In Vitro Antimicrobial Assessment, and Molecular Docking Investigations of Some Derived Compounds From Porphyrins.Journal of fluorescence · 2026Article
- Amide-functionalized cholic acid hybrids: design, bioactivity, and computational analysis.RSC advances · 2026Article
- Silver-LoadedMarine drugs · 2026Article
- Orthogonal Biosynthesis of Pyrrolamides through Dehydration by a Pathway-Specific Glycoside Hydrolase-Like Enzyme in Gram-Positive Bacteria.Journal of the American Chemical Society · 2026Article
- Chemical Profiling, Ampicillin Interaction Patterns, and Exploratory Molecular Docking ofInternational journal of molecular sciences · 2026Article
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- Integrated Virtual Screening for Anti-Caries Compounds from Neem: Dual-Target Inhibition of Biofilm Formation and Bacterial DNA Replication.Biomedicines · 2025Article
- Recent advancements in the development of next-generation dual-targeting antibacterial agents.RSC medicinal chemistry · 2025Review
- Synthesis and Antimicrobial Evaluation of (+)-Neoisopulegol-Based Amino and Thiol Adducts.International journal of molecular sciences · 2025Article
- Inhibitory Effect of Non-Saccharomyces Starmerella bacillaris CC-PT4 Isolated from Grape on MRSA Growth and Biofilm.Probiotics and antimicrobial proteins · 2025Article
- New Insights into the Antibacterial Activity of Hydroxytyrosol Extracted from Olive Leaves: Molecular Docking Simulations of its Antibacterial Mechanisms.Chemistry & biodiversity · 2025Article
- Phytochemical Characterization and Antibacterial Activity of Carthamus Caeruleus L. Aqueous Extracts: In Vitro and In Silico Molecular Docking Studies.Chemistry & biodiversity · 2025Article
- Unlocking the Potential of Pyrrole: Recent Advances in New Pyrrole-Containing Compounds with Antibacterial Potential.International journal of molecular sciences · 2024Review
- Novel Thiazole Derivatives Containing Imidazole and Furan Scaffold: Design, Synthesis, Molecular Docking, Antibacterial, and Antioxidant Evaluation.Molecules (Basel, Switzerland) · 2024Article
- Recent Development of DNA Gyrase Inhibitors: An Update.Mini reviews in medicinal chemistry · 2024Review
- Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Thiosemicarbazide Derivatives Decrease the ATPase Activity ofInternational journal of molecular sciences · 2021Article
- Synthesis of Computationally Designed 2,5(6)-Benzimidazole Derivatives via Pd-Catalyzed Reactions for PotentialMolecules (Basel, Switzerland) · 2021Article
- Exploring the Chemical Space of Benzothiazole-Based DNA Gyrase B Inhibitors.ACS medicinal chemistry letters · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA gyrase is an essential enzyme in bacteria, and its inhibition results in the disruption of DNA synthesis and, subsequently, cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase. These compounds were identified by a fragment-based lead generation (FBLG) approach using nuclear magnetic resonance (NMR) screening to identify low-molecular-weight compounds that bind to the ATP pocket of DNA gyrase. A pyrrole hit with a binding constant of 1 mM formed the basis of the design and synthesis of a focused library of compounds that resulted in the rapid identification of a lead compound that inhibited DNA gyrase with a 50% inhibitory concentration (IC(50)) of 3 μM. The potency of the lead compound was further optimized by utilizing iterative X-ray crystallography to yield DNA gyrase inhibitors that also displayed antibacterial activity. Spontaneous mutants were isolated in Staphylococcus aureus by plating on agar plates containing pyrrolamide 4 at the MIC. The resistant variants displayed 4- to 8-fold-increased MIC values relative to the parent strain. DNA sequencing revealed two independent point mutations in the pyrrolamide binding region of the gyrB genes from these variants, supporting the hypothesis that the mode of action of these compounds was inhibition of DNA gyrase. Efficacy of a representative pyrrolamide was demonstrated against Streptococcus pneumoniae in a mouse lung infection model. These data demonstrate that the pyrrolamides are a novel class of DNA gyrase inhibitors with the potential to deliver future antibacterial agents targeting multiple clinical indications.
Indexed as
Identifiers
What OpenQuestion holds
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.