ArticleScientific reports2017
MEPicides: potent antimalarial prodrugs targeting isoprenoid biosynthesis.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Expanding the Chemical Space of Reverse Fosmidomycin Analogs.ACS medicinal chemistry letters · 2025Article
- Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).bioRxiv : the preprint server for biology · 2024Article
- Design and synthesis of non-hydroxamate lipophilic inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR):RSC advances · 2024Article
- A picomolar inhibitor of theAntimicrobial agents and chemotherapy · 2024Article
- Inhibition of DXR in the MEP pathway with lipophilicRSC medicinal chemistry · 2024Article
- MEPicides: α,β-unsaturated FosmidomycinACS infectious diseases · 2023Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Synthesis, Structure−Activity Relationships, and Parasitological Profiling of Brussonol Derivatives as New Plasmodium falciparum InhibitorsPharmaceuticals (Basel, Switzerland) · 2022Article
- Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.The Journal of biological chemistry · 2022Article
- Article
- Antimicrobial Prodrug Activation by the Staphylococcal Glyoxalase GloB.ACS infectious diseases · 2020Article
- Synthesis and Antiplasmodial Activity of Novel Fosmidomycin Derivatives and Conjugates with Artemisinin and Aminochloroquinoline.Molecules (Basel, Switzerland) · 2020Article
- Potent, specific MEPicides for treatment of zoonotic staphylococci.PLoS pathogens · 2020Article
- Phosphonate prodrugs: an overview and recent advances.Future medicinal chemistry · 2019Review
- Determination of the Activity of 1-Deoxy-D-Xylulose 5-Phosphate Synthase by Pre-column Derivatization-HPLC Using 1,2-Diamino-4,5-Methylenedioxybenzene as a Derivatizing Reagent.The protein journal · 2019Article
- MEPicides: α,β-Unsaturated Fosmidomycin Analogues as DXR Inhibitors against Malaria.Journal of medicinal chemistry · 2018Article
- Synthesis and Evaluation of Fluoroalkyl Phosphonyl Analogues of 2- C-Methylerythritol Phosphate as Substrates and Inhibitors of IspD from Human Pathogens.The Journal of organic chemistry · 2018Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
The emergence of Plasmodium falciparum resistant to frontline therapeutics has prompted efforts to identify and validate agents with novel mechanisms of action. MEPicides represent a new class of antimalarials that inhibit enzymes of the methylerythritol phosphate (MEP) pathway of isoprenoid biosynthesis, including the clinically validated target, deoxyxylulose phosphate reductoisomerase (Dxr). Here we describe RCB-185, a lipophilic prodrug with nanomolar activity against asexual parasites. Growth of P. falciparum treated with RCB-185 was rescued by isoprenoid precursor supplementation, and treatment substantially reduced metabolite levels downstream of the Dxr enzyme. In addition, parasites that produced higher levels of the Dxr substrate were resistant to RCB-185. Notably, environmental isolates resistant to current therapies remained sensitive to RCB-185, the compound effectively treated sexually-committed parasites, and was both safe and efficacious in malaria-infected mice. Collectively, our data demonstrate that RCB-185 potently and selectively inhibits Dxr in P. falciparum, and represents a promising lead compound for further drug development.
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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.