ArticleScientific reports2013
Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase.
Article in Scientific reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 81 citations in OpenAlex.
- The ZN domain acts as a dynamic switch coordinating multiple-step aminoacylation in bacterial leucyl-tRNA synthetase.Nucleic acids research · 2026Article
- Mutational basis of ceftazidime-borrelidin A collateral sensitivity in Escherichia coli.G3 (Bethesda, Md.) · 2026Article
- Selectivity of the Time-DependentACS chemical biology · 2025Article
- Genome-wide Screening of the Escherichia coli Keio Knockout Collection Identifies Genetic Determinants of Epetraborole Hypersusceptibility.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Trends on Potential Boron-containing Drugs by Advancements in Ligand-protein Crystals Complexes.Current medicinal chemistry · 2025Review
- Targeting a microbiotaScience advances · 2024Article
- Exploiting thiol-functionalized benzosiloxaboroles for achieving diverse substitution patterns - synthesis, characterization and biological evaluation of promising antibacterial agents.RSC medicinal chemistry · 2024Article
- Laboratory Evolution of Antimicrobial Resistance in Bacteria to Develop Rational Treatment Strategies.Antibiotics (Basel, Switzerland) · 2024Review
- New antibacterial candidates against Acinetobacter baumannii discovered by in silico-driven chemogenomics repurposing.PloS one · 2024Article
- Aromatic Diboronic Acids as Effective KPC/AmpC Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- DS86760016, a Leucyl-tRNA Synthetase Inhibitor, Is Active against Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2023Article
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Design, Synthesis and Antimicrobial Evaluation of NewInternational journal of molecular sciences · 2023Article
- Adenosine-Dependent Activation Mechanism of Prodrugs Targeting an Aminoacyl-tRNA Synthetase.Journal of the American Chemical Society · 2023Article
- Oxazoline scaffold in synthesis of benzosiloxaboroles and related ring-expanded heterocycles: diverse reactivity, structural peculiarities and antimicrobial activity.RSC advances · 2022Article
- Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective.Molecules (Basel, Switzerland) · 2022Review
- Molecular targets for antifungals in amino acid and protein biosynthetic pathways.Amino acids · 2021Review
- Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series.Microorganisms · 2021Article
- Organoboron Compounds: Effective Antibacterial and Antiparasitic Agents.Molecules (Basel, Switzerland) · 2021Review
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptococcus pneumoniae causes bacterial pneumonia with high mortality and morbidity. The emergency of multidrug-resistant bacteria threatens the treatment of the disease. Leucyl-tRNA synthetase (LeuRS) plays an essential role in cellular translation and is an attractive drug target for antimicrobial development. Here we report the compound ZCL039, a benzoxaborole-based derivative of AN2690, as a potent anti-pneumococcal agent that inhibits S. pneumoniae LeuRS (SpLeuRS) activity. We show using kinetic, biochemical analyses combined with the crystal structure of ZCL039-AMP in complex with the separated SpLeuRS editing domain, that ZCL039 binds to the LeuRS editing active site which requires the presence of tRNA(Leu), and employs an uncompetitive inhibition mechanism. Further docking models establish that ZCL039 clashes with the eukaryal/archaeal specific insertion I4ae helix within editing domains. These findings demonstrate the potential of benzoxaboroles as effective LeuRS inhibitors for pneumococcus infection therapy, and provide future structure-guided drug design and optimization.
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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.