ArticleAntimicrobial agents and chemotherapy2013
An FtsZ-targeting prodrug with oral antistaphylococcal efficacy in vivo.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 58 citations in OpenAlex.
- Antibacterial drug discovery: challenges and preclinical promises from synthetic small molecules.Chemical Society reviews · 2026Review
- Development of Broad-Spectrum Antimicrobial Peptides through the Conjugation of FtsZ-Binding and Cell-Penetrating Peptides.ACS infectious diseases · 2025Article
- Identification of a New FtsZ Inhibitor by Virtual Screening, Mechanistic Insights, and Structure-Activity Relationship Analyses.ACS infectious diseases · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- Targeting Bacterial Cell Division with Benzodioxane-Benzamide FtsZ Inhibitors as a Novel Strategy to Fight Gram-Positive Ovococcal Pathogens.International journal of molecular sciences · 2025Article
- Article
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Computational docking of FtsZ: Survey of promising antibiotic compounds.Biochemistry and biophysics reports · 2024Article
- A New Guanidine-Core Small-Molecule Compound as a Potential Antimicrobial Agent against Resistant Bacterial Strains.Antibiotics (Basel, Switzerland) · 2024Article
- A FtsZ Inhibitor That Can Utilize Siderophore-Ferric Iron Uptake Transporter Systems for Activity against Gram-Negative Bacterial Pathogens.Antibiotics (Basel, Switzerland) · 2024Article
- Design and Synthesis of Novel Antimicrobial Agents.Antibiotics (Basel, Switzerland) · 2023Review
- Structural and Antibacterial Characterization of a New Benzamide FtsZ Inhibitor with Superior Bactericidal Activity and In Vivo Efficacy Against Multidrug-ResistantACS chemical biology · 2023Article
- Models versus pathogens: how conserved is the FtsZ in bacteria?Bioscience reports · 2023Review
- Evaluation of 2,6-difluoro-3-(oxazol-2-ylmethoxy)benzamide chemotypes as Gram-negative FtsZ inhibitors.The Journal of antibiotics · 2022Article
- Impact of FtsZ Inhibition on the Localization of the Penicillin Binding Proteins in Methicillin-Resistant Staphylococcus aureus.Journal of bacteriology · 2021Article
- Antimicrobial Action and Reversal of Resistance in MRSA by Difluorobenzamide Derivatives Targeted at FtsZ.Antibiotics (Basel, Switzerland) · 2020Article
- Antibacterial Prodrugs to Overcome Bacterial Resistance.Molecules (Basel, Switzerland) · 2020Review
- Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ.Antibiotics (Basel, Switzerland) · 2020Review
- Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens.Scientific reports · 2019Article
- Phenanthrene Antibiotic Targets Bacterial Membranes and KillsFrontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bacterial cell division protein FtsZ represents a novel antibiotic target that has yet to be exploited clinically. The benzamide PC190723 was among the first FtsZ-targeting compounds to exhibit in vivo efficacy in a murine infection model system. Despite its initial promise, the poor formulation properties of the compound have limited its potential for clinical development. We describe here the development of an N-Mannich base derivative of PC190723 with enhanced drug-like properties and oral in vivo efficacy. The N-Mannich base derivative (TXY436) is ∼100-fold more soluble than PC190723 in an acidic aqueous vehicle (10 mM citrate, pH 2.6) suitable for oral in vivo administration. At physiological pH (7.4), TXY436 acts as a prodrug, converting to PC190723 with a conversion half-life of 18.2 ± 1.6 min. Pharmacokinetic analysis following intravenous administration of TXY436 into mice yielded elimination half-lives of 0.26 and 0.96 h for the TXY436 prodrug and its PC190723 product, respectively. In addition, TXY436 was found to be orally bioavailable and associated with significant extravascular distribution. Using a mouse model of systemic infection with methicillin-sensitive Staphylococcus aureus or methicillin-resistant S. aureus, we show that TXY436 is efficacious in vivo upon oral administration. In contrast, the oral administration of PC190723 was not efficacious. Mammalian cytotoxicity studies of TXY436 using Vero cells revealed an absence of toxicity up to compound concentrations at least 64 times greater than those associated with antistaphylococcal activity. These collective properties make TXY436 a worthy candidate for further investigation as a clinically useful agent for the treatment of staphylococcal 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.