ArticleAntimicrobial agents and chemotherapy2016
Cryptosporidium and Toxoplasma Parasites Are Inhibited by a Benzoxaborole Targeting Leucyl-tRNA Synthetase.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 67 citations in OpenAlex.
- The ZN domain acts as a dynamic switch coordinating multiple-step aminoacylation in bacterial leucyl-tRNA synthetase.Nucleic acids research · 2026Article
- A Novel Class of Orally Bioavailable Phenylglycine-Benzoxaborole Conjugates with Antimalarial Activity and Potentially Novel Mechanism of Action.ACS medicinal chemistry letters · 2026Article
- Selectivity of the Time-DependentACS chemical biology · 2025Article
- In vitro molecular assessment ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Article
- Trends on Potential Boron-containing Drugs by Advancements in Ligand-protein Crystals Complexes.Current medicinal chemistry · 2025Review
- Molecular pathogenesis of Cryptosporidium and advancements in therapeutic interventions.Parasite (Paris, France) · 2025Review
- Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium.Molecular and biochemical parasitology · 2024Article
- Structure-activity relationship of BMS906024 derivatives for Cryptosporidium parvum growth inhibition.Bioorganic & medicinal chemistry letters · 2023Article
- The 4-Aminomethylphenoxy-Benzoxaborole AN3057 as a Potential Treatment Option for Primary Amoebic Meningoencephalitis.Antimicrobial agents and chemotherapy · 2023Article
- Adenosine-Dependent Activation Mechanism of Prodrugs Targeting an Aminoacyl-tRNA Synthetase.Journal of the American Chemical Society · 2023Article
- Mode of action studies confirm on-target engagement of lysyl-tRNA synthetase inhibitor and lead to new selection marker forFrontiers in cellular and infection microbiology · 2023Article
- Preliminary Structure-Activity Relationship Study of the MMV Pathogen Box Compound MMV675968 (2,4-Diaminoquinazoline) Unveils Novel Inhibitors ofMolecules (Basel, Switzerland) · 2022Article
- Label-free quantitative proteomic analysis of ethanamizuril-resistant versus -sensitive strains of Eimeria tenella.Parasites & vectors · 2022Article
- Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development.PLoS pathogens · 2022Article
- Lyme disease transmission by severely impaired ticks.Open biology · 2022Article
- An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives.Frontiers in cellular and infection microbiology · 2022Review
- Organoboron Compounds: Effective Antibacterial and Antiparasitic Agents.Molecules (Basel, Switzerland) · 2021Review
- Amino Acid Metabolism in Apicomplexan Parasites.Metabolites · 2021Review
- Bicyclic azetidines kill the diarrheal pathogenScience translational medicine · 2020Article
- Exploiting evolutionary trade-offs for posttreatment management of drug-resistant populations.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children and immunocompromised individuals, with the only FDA-approved drug treatment currently being nitazoxanide. The existing therapies for toxoplasmosis, an important pathology in immunocompromised individuals and pregnant women, also have serious limitations. With the aim of developing alternative therapeutic options to address these health problems, we tested a number of benzoxaboroles, boron-containing compounds shown to be active against various infectious agents, for inhibition of the growth of Cryptosporidium parasites in mammalian cells. A 3-aminomethyl benzoxaborole, AN6426, with activity in the micromolar range and with activity comparable to that of nitazoxanide, was identified and further characterized using biophysical measurements of affinity and crystal structures of complexes with the editing domain of Cryptosporidium leucyl-tRNA synthetase (LeuRS). The same compound was shown to be active against Toxoplasma parasites, with the activity being enhanced in the presence of norvaline, an amino acid that can be mischarged by LeuRS. Our observations are consistent with AN6426 inhibiting protein synthesis in both Cryptosporidium and Toxoplasma by forming a covalent adduct with tRNA(Leu) in the LeuRS editing active site and suggest that further exploitation of the benzoxaborole scaffold is a valid strategy to develop novel, much needed antiparasitic agents.
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