ArticleBioorganic & medicinal chemistry2010
Phosphoramidates of 2'-beta-D-arabinouridine (AraU) as phosphate prodrugs; design, synthesis, in vitro activity and metabolism.
Article in Bioorganic & medicinal chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Production of Value-Added Arabinofuranosyl Nucleotide Analogues from Nucleoside by an In Vitro Enzymatic Synthetic Biosystem.Biomolecules · 2024Article
- Biosynthesis of Arabinoside from Sucrose and Nucleobase via a Novel Multi-Enzymatic Cascade.Biomolecules · 2024Article
- Developing nucleoside tailoring strategies against SARS-CoV-2 via ribonuclease targeting chimera.Science advances · 2024Article
- PINK1-Dependent Mitophagy Inhibits Elevated Ubiquitin Phosphorylation Caused by Mitochondrial Damage.Journal of medicinal chemistry · 2023Article
- Aryloxy Diester Phosphonamidate Prodrugs of Phosphoantigens (ProPAgens) as Potent Activators of Vγ9/Vδ2 T-Cell Immune Responses.Journal of medicinal chemistry · 2020Article
- Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues.Molecules (Basel, Switzerland) · 2020Review
- The ProTide Prodrug Technology: From the Concept to the Clinic.Journal of medicinal chemistry · 2018Review
- Synthesis and Biological Evaluation of ( E)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses.Journal of medicinal chemistry · 2018Article
- Kinetin Riboside and Its ProTides Activate the Parkinson's Disease Associated PTEN-Induced Putative Kinase 1 (PINK1) Independent of Mitochondrial Depolarization.Journal of medicinal chemistry · 2017Article
- Metabolism, Biochemical Actions, and Chemical Synthesis of Anticancer Nucleosides, Nucleotides, and Base Analogs.Chemical reviews · 2016Review
- Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy.Molecular genetics and metabolism · 2015Article
- Prodrugs of phosphonates and phosphates: crossing the membrane barrier.Topics in current chemistry · 2015Review
- Synthesis of nucleoside phosphate and phosphonate prodrugs.Chemical reviews · 2014Review
- Phosphoramidates and phosphonamidates (ProTides) with antiviral activity.Antiviral chemistry & chemotherapyReview
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7 authors.
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Abstract
2'-Beta-D-arabinouridine (AraU), the uridine analogue of the anticancer agent AraC, was synthesized and evaluated for antiviral activity and cytotoxicity. In addition, a series of AraU monophosphate prodrugs in the form of triester phosphoramidates (ProTides) were also synthesized and tested against a range of viruses, leukaemia and solid tumour cell lines. Unfortunately, neither the parent compound (AraU) nor any of its ProTides showed antiviral activity, nor potent inhibitory activity against any of the cancer cell lines. Therefore, the metabolism of AraU phosphoramidates to release AraU monophosphate was investigated. The results showed carboxypeptidase Y, hog liver esterase and crude CEM tumor cell extracts to hydrolyse the ester motif of phosphoramidates with subsequent loss of the aryl group, while molecular modelling studies suggested that the AraU l-alanine aminoacyl phosphate derivative might not be a good substrate for the phosphoramidase enzyme Hint-1. These findings are in agreement with the observed disappearance of intact prodrug and concomitant appearance of the corresponding phosphoramidate intermediate derivative in CEM cell extracts without measurable formation of araU monophosphate. These findings may explain the poor antiviral/cytostatic potential of the prodrugs.
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