ArticlePLoS biology2020
Rational design of balanced dual-targeting antibiotics with limited resistance.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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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
27 citing papers in PubMed, 41 citations in OpenAlex.
- Trends towards multidrug-resistant bacteria: heterocyclic compounds containing antimicrobial agents: review.RSC advances · 2026Review
- Predicting resistance evolution to guide antibiotic development.Nature reviews. Microbiology · 2026Review
- Repurposing Azeliragon as a novel antibacterial agent against methicillin-resistant Staphylococcus aureus via combined membrane phospholipids and cell wall targeting.Communications biology · 2026Article
- Article
- Cold atmospheric plasma mediates antibiofilm activity and sensitization to further plasma and antibiotic challenges againstFEMS microbes · 2026Article
- Modulators of gene amplification alter evolution of antibiotic resistance in Staphylococcus aureus.PLoS genetics · 2025Article
- Antimicrobial and Antibiofilm Activities of Some Antioxidant 3,4-Dihydroxyphenyl-Thiazole-Coumarin Hybrid Compounds: In Silico and In Vitro Evaluation.Antibiotics (Basel, Switzerland) · 2025Article
- Recent advancements in the development of next-generation dual-targeting antibacterial agents.RSC medicinal chemistry · 2025Review
- Exploring the principles behind antibiotics with limited resistance.Nature communications · 2025Article
- ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.Nature microbiology · 2025Article
- Methyl 2-amino-4-(morpholin-4-yl)benzo[IUCrData · 2025Article
- Unlocking the Potential of Pyrrole: Recent Advances in New Pyrrole-Containing Compounds with Antibacterial Potential.International journal of molecular sciences · 2024Review
- Special Issue: "Rational Design and Synthesis of Bioactive Molecules".International journal of molecular sciences · 2024Article
- NewRSC advances · 2024Article
- Benzothiazole DNA gyrase inhibitors and their conjugates with siderophore mimics: design, synthesis and evaluation.RSC advances · 2024Article
- Discovery of new Schiff bases of the disalicylic acid scaffold as DNA gyrase and topoisomerase IV inhibitors endowed with antibacterial properties.Frontiers in chemistry · 2024Article
- Antimicrobial resistance expansion in pathogens: a review of current mitigation strategies and advances towards innovative therapy.JAC-antimicrobial resistance · 2023Review
- Exploring the 5-Substituted 2-Aminobenzothiazole-Based DNA Gyrase B Inhibitors Active against ESKAPE Pathogens.ACS omega · 2023Article
- Efflux pump gene amplifications bypass necessity of multiple target mutations for resistance against dual-targeting antibiotic.Nature communications · 2023Article
- An Update Review of Approaches to Multiple Action-Based Antibacterials.Antibiotics (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds, ULD1 and ULD2, belonging to a novel chemical class, almost equipotently inhibit bacterial DNA gyrase and topoisomerase IV complexes and interact with multiple evolutionary conserved amino acids in the ATP-binding pockets of their target proteins. ULD1 and ULD2 are excellently potent against a broad range of gram-positive bacteria. Notably, the efficacy of these compounds was tested against a broad panel of multidrug-resistant Staphylococcus aureus clinical strains. Antibiotics with clinical relevance against staphylococcal infections fail to inhibit a significant fraction of these isolates, whereas both ULD1 and ULD2 inhibit all of them (minimum inhibitory concentration [MIC] ≤1 μg/mL). Resistance mutations against these compounds are rare, have limited impact on compound susceptibility, and substantially reduce bacterial growth. Based on their efficacy and lack of toxicity demonstrated in murine infection models, these compounds could translate into new therapies against multidrug-resistant bacterial infections.
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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.