ReviewAnnals of the New York Academy of Sciences2019
The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics.
Review in Annals of the New York Academy of Sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 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
116 citing papers in PubMed, 231 citations in OpenAlex.
- Random Forest Modeling to Predict Small Molecule Accumulation in Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- Antibacterial drug discovery: challenges and preclinical promises from synthetic small molecules.Chemical Society reviews · 2026Review
- Structure-Activity Relationship Studies for 1,3,4-Thiadiazole-Based Bacterial Carbonic Anhydrase Inhibitors withJournal of medicinal chemistry · 2026Article
- Phosphonamidates Integrating Sterically Hindered Phenols with Membrane-Active Cations: A Redox-Activated Approach to Antimicrobial Agents.International journal of molecular sciences · 2026Article
- Zwitterionic Penicillin-Derived Sulfone Inhibitor for Combating β-Lactamase-Mediated Antibiotic Resistance.ChemMedChem · 2026Article
- Natural Antimicrobials from Plants Used as Food Preservatives.Foods (Basel, Switzerland) · 2026Review
- Targeting of the Gram-Negative Outer Membrane for Antibiotic Discovery and Potentiation.ACS infectious diseases · 2026Review
- Prevalence of pre-hospital antibiotic exposure and its associated factors among pediatric population: a cross-sectional study.BMC pediatrics · 2026Article
- A Ratiometric pH Sensor for Gram-Positive and Gram-Negative Bacteria.Journal of the American Chemical Society · 2026Article
- The Quantification of Drug Accumulation within Gram-Negative Bacteria.ACS infectious diseases · 2026Article
- High-throughput triazole-based combinatorial click chemistry for the synthesis and identification of functional metal complexes.Nature communications · 2025Article
- Discovery of 5‑Chlorotryptophan-Containing Antibiotics through Metabologenomics-Assisted High-Throughput Screening.JACS Au · 2025Article
- Antibiotic Resistance Crisis: From Bacterial Bioprospecting to Artificial Intelligence.Environmental microbiology reports · 2025Review
- From Obscurity to Opportunity: LpxH Emerges as a Promising Antibiotic Target in the Battle against Gram-Negative Pathogens.ACS infectious diseases · 2025Review
- Retargeting Gram-Positive-Only Adarotene-Derived Antibacterials to Broad-Spectrum Antibiotics.Antibiotics (Basel, Switzerland) · 2025Article
- Article
- Measurement and prediction of small molecule retention by Gram-negative bacteria based on a large-scale LC/MS screen.Scientific reports · 2025Article
- Convergent evolution of antibiotic resistance mechanisms between pyrrolobenzodiazepines and albicidin in multidrug resistant Klebsiella pneumoniae.npj antimicrobials and resistance · 2025Article
- Rational search for natural antimicrobial compounds: relevance of sesquiterpene lactones.Natural products and bioprospecting · 2025Article
- Synthesis, antimicrobial evaluation, HPLC-based compound accumulation and docking studies of 2-methoxybenzoyl thioureas.Future medicinal chemistry · 2025Article
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Multidrug resistant Gram-negative bacterial infections are on the rise, and there is a lack of new classes of drugs to treat these pathogens. This drug shortage is largely due to the challenge of finding antibiotics that can permeate and persist inside Gram-negative species. Efforts to understand the molecular properties that enable certain compounds to accumulate in Gram-negative bacteria based on retrospective studies of known antibiotics have not been generally actionable in the development of new antibiotics. A recent assessment of the ability of >180 diverse small molecules to accumulate in Escherichia coli led to predictive guidelines for compound accumulation in E. coli. These "eNTRy rules" state that compounds are most likely to accumulate if they contain a nonsterically encumbered ionizable Nitrogen (primary amines are the best), have low Three-dimensionality (globularity ≤ 0.25), and are relatively Rigid (rotatable bonds ≤ 5). In this review, we look back through 50+ years of antibacterial research and 1000s of derivatives and assess this historical data set through the lens of these predictive guidelines. The results are consistent with the eNTRy rules, suggesting that the eNTRy rules may provide an actionable and general roadmap for the conversion of Gram-positive-only compounds into broad-spectrum antibiotics.
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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.