ArticleChemistry & biology2012
Acyclic immucillin phosphonates: second-generation inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase.
Article in Chemistry & biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 68 citations in OpenAlex.
- Gas Phase Studies of Purine Base Analogs: Intrinsic Properties and Hypoxanthine-Guanine-(Xanthine) Phosphoribosyltransferase (HG(X)PRT).The Journal of organic chemistry · 2026Article
- C1'-Branched Acyclic Nucleoside Phosphonates as Inhibitors of Plasmodium Falciparum 6-Oxopurine Phosphoribosyltransferase.ChemMedChem · 2025Article
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Recent Synthesis of Nucleoside Phosphonate Analogs Using Olefin Cross-metathesis.Current medicinal chemistry · 2025Review
- Development of Prolinol Containing Inhibitors of Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase: Rational Structure-Based Drug Design.Journal of medicinal chemistry · 2024Article
- Kinetic and Structural Characterization ofBiochemistry · 2023Article
- Inhibition and Mechanism ofACS chemical biology · 2022Article
- The design of protozoan phosphoribosyltransferase inhibitors containing non-charged phosphate mimic residues.Bioorganic & medicinal chemistry · 2022Article
- Kinetic Characterization and Inhibition ofBiochemistry · 2022Article
- Inhibition of the futalosine pathway for menaquinone biosynthesis suppresses Chlamydia trachomatis infection.FEBS letters · 2021Article
- Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action.Molecular biology · 2021Article
- Overview of Biologically Active Nucleoside Phosphonates.Frontiers in chemistry · 2020Review
- Enzymatic Transition States and Drug Design.Chemical reviews · 2018Review
- Expedient synthesis and biological evaluation of alkenyl acyclic nucleoside phosphonate prodrugs.Bioorganic & medicinal chemistry · 2018Article
- Synthesis and antiplasmodial activity of purine-basedMedChemComm · 2018Article
- Evaluation of the Trypanosoma brucei 6-oxopurine salvage pathway as a potential target for drug discovery.PLoS neglected tropical diseases · 2018Article
- Kinetic Isotope Effects and Transition State Structure for Hypoxanthine-Guanine-Xanthine Phosphoribosyltransferase from Plasmodium falciparum.Biochemistry · 2017Article
- Crystal structures and inhibition of Trypanosoma brucei hypoxanthine-guanine phosphoribosyltransferase.Scientific reports · 2016Article
- Purine import into malaria parasites as a target for antimalarial drug development.Annals of the New York Academy of Sciences · 2015Review
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
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Authors and funding
10 authors at 1 institution in 1 country.
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Abstract
Plasmodium falciparum, the primary cause of deaths from malaria, is a purine auxotroph and relies on hypoxanthine salvage from the host purine pool. Purine starvation as an antimalarial target has been validated by inhibition of purine nucleoside phosphorylase. Hypoxanthine depletion kills Plasmodium falciparum in cell culture and in Aotus monkey infections. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from P. falciparum is required for hypoxanthine salvage by forming inosine 5'-monophosphate, a branchpoint for all purine nucleotide synthesis in the parasite. Here, we present a class of HGXPRT inhibitors, the acyclic immucillin phosphonates (AIPs), and cell permeable AIP prodrugs. The AIPs are simple, potent, selective, and biologically stable inhibitors. The AIP prodrugs block proliferation of cultured parasites by inhibiting the incorporation of hypoxanthine into the parasite nucleotide pool and validates HGXPRT as a target in malaria.
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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.