ArticleNature communications2022
Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Minimum Inoculum of Resistance Assay for Evaluating Antitoxoplasmosis Compounds That Target Phenylalanine tRNA Synthetase.ACS infectious diseases · 2026Article
- Lead Optimization of TgCDPK1 Inhibitors for the Treatment of Toxoplasmosis.Journal of medicinal chemistry · 2026Article
- Legacy 4(1ACS infectious diseases · 2026Article
- Minimum inoculum of resistance assay for evaluating for anti-toxoplasmosis compounds that target phenyl alanine tRNA synthetase.bioRxiv : the preprint server for biology · 2026Article
- Parasitic diseases in heart transplantation: challenges of Toxoplasmosis and Chagas Disease.JHLT open · 2026Review
- Improved Bicyclic Pyrrolidine Analogues InhibitJournal of medicinal chemistry · 2025Article
- High-Throughput Repurposing Screen Reveals Compounds with Activity againstACS infectious diseases · 2025Article
- Novel Drug Targets for the Bradyzoite Form ofResearch and reports in tropical medicine · 2025Review
- Article
- High Throughput Repurposing Screen Reveals Compounds with Activity AgainstbioRxiv : the preprint server for biology · 2024Article
- ATP mimetics targeting prolyl-tRNA synthetases as a new avenue for antimalarial drug development.iScience · 2024Article
- Investigating Antiprotozoal Chemotherapies with Novel Proteomic Tools-Chances and Limitations: A Critical Review.International journal of molecular sciences · 2024Review
- Bicyclic Pyrrolidine Inhibitors ofACS infectious diseases · 2024Article
- Bicyclic pyrrolidine inhibitors ofbioRxiv : the preprint server for biology · 2024Article
- Formulation and evaluation of atovaquone-loaded macrophage-derived exosomes againstMicrobiology spectrum · 2024Article
- Genome-wide and targeted CRISPR screens identify RNF213 as a mediator of interferon gamma-dependent pathogen restriction in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- The determinants regulatingFrontiers in microbiology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Toxoplasma gondii commonly infects humans and while most infections are controlled by the immune response, currently approved drugs are not capable of clearing chronic infection in humans. Hence, approximately one third of the world's human population is at risk of reactivation, potentially leading to severe sequelae. To identify new candidates for treating chronic infection, we investigated a series of compounds derived from diversity-oriented synthesis. Bicyclic azetidines are potent low nanomolar inhibitors of phenylalanine tRNA synthetase (PheRS) in T. gondii, with excellent selectivity. Biochemical and genetic studies validate PheRS as the primary target of bicyclic azetidines in T. gondii, providing a structural basis for rational design of improved analogs. Favorable pharmacokinetic properties of a lead compound provide excellent protection from acute infection and partial protection from chronic infection in an immunocompromised mouse model of toxoplasmosis. Collectively, PheRS inhibitors of the bicyclic azetidine series offer promise for treatment of chronic toxoplasmosis.
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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.