Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
| Autor: | Jennifer M. Mason, Keith Clinch, Douglas R. Crump, Gary B. Evans, Keith Z. Hazleton, Vern L. Schramm, Peter C. Tyler |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Inosine monophosphate
Clinical Biochemistry Plasmodium falciparum Pharmaceutical Science Biochemistry Article chemistry.chemical_compound Antimalarials Drug Discovery parasitic diseases Humans Pentosyltransferases Enzyme Inhibitors Purine metabolism Molecular Biology Nucleotide salvage Hypoxanthine Aza Compounds biology Chemistry Organic Chemistry Nucleosides biology.organism_classification Xanthine phosphoribosyltransferase Kinetics Hypoxanthine-guanine phosphoribosyltransferase biology.protein Molecular Medicine Phosphoribosyltransferase Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry. 21(17) |
| ISSN: | 1464-3391 |
| Popis: | The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C- nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect