ArticleProceedings of the National Academy of Sciences of the United States of America2014
Analogs of natural aminoacyl-tRNA synthetase inhibitors clear malaria in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 82 citations in OpenAlex.
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- Identifying antimalarials that disrupt malaria parasite transmission when fed to the mosquito.International journal for parasitology · 2025Article
- Harnessing Actinobacteria secondary metabolites for tuberculosis drug discovery: Historical trends, current status and future outlooks.Natural products and bioprospecting · 2025Review
- A high content imaging assay for identification of specific inhibitors of nativeAntimicrobial agents and chemotherapy · 2024Article
- Antimalarial activity of borrelidin and fumagilin inOpen veterinary journal · 2024Article
- A high content imaging assay for identification of specific inhibitors of nativebioRxiv : the preprint server for biology · 2024Article
- Discovery of Malarial Threonyl tRNA Synthetase Inhibitors by Screening of a Focused Fragment Library.ACS medicinal chemistry letters · 2024Article
- Structure-based identification of salicylic acid derivatives as malarial threonyl tRNA-synthetase inhibitors.PloS one · 2024Article
- Single-cell quantitative bioimaging ofmSphere · 2023Article
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Cytoplasmic isoleucyl tRNA synthetase as an attractive multistage antimalarial drug target.Science translational medicine · 2023Article
- Toolkit of Approaches To Support Target-Focused Drug Discovery forACS infectious diseases · 2022Article
- High-Throughput Screening Platform To Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria.Antimicrobial agents and chemotherapy · 2022Article
- Rational Design of Hit Compounds TargetingACS omega · 2021Article
- Structural analyses of the malaria parasite aminoacyl-tRNA synthetases provide new avenues for antimalarial drug discovery.Protein science : a publication of the Protein Society · 2021Review
- Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.International journal of molecular sciences · 2021Review
- Melatonin action in Plasmodium infection: Searching for molecules that modulate the asexual cycle as a strategy to impair the parasite cycle.Journal of pineal research · 2021Review
- Recent Development of Aminoacyl-tRNA Synthetase Inhibitors for Human Diseases: A Future Perspective.Biomolecules · 2020Review
- Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor.Nucleic acids research · 2020Article
- In silico assessment of natural products and approved drugs as potential inhibitory scaffolds targeting aminoacyl-tRNA synthetases from3 Biotech · 2020Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
Malaria remains a major global health problem. Emerging resistance to existing antimalarial drugs drives the search for new antimalarials, and protein translation is a promising pathway to target. Here we explore the potential of the aminoacyl-tRNA synthetase (ARS) family as a source of antimalarial drug targets. First, a battery of known and novel ARS inhibitors was tested against Plasmodium falciparum cultures, and their activities were compared. Borrelidin, a natural inhibitor of threonyl-tRNA synthetase (ThrRS), stands out for its potent antimalarial effect. However, it also inhibits human ThrRS and is highly toxic to human cells. To circumvent this problem, we tested a library of bioengineered and semisynthetic borrelidin analogs for their antimalarial activity and toxicity. We found that some analogs effectively lose their toxicity against human cells while retaining a potent antiparasitic activity both in vitro and in vivo and cleared malaria from Plasmodium yoelii-infected mice, resulting in 100% mice survival rates. Our work identifies borrelidin analogs as potent, selective, and unexplored scaffolds that efficiently clear malaria both in vitro and in vivo.
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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.