Synthesis of branched 9-[2-(2-phosphonoethoxy)ethyl]purines as a new class of acyclic nucleoside phosphonates which inhibit Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19666228
DOI
10.1016/j.bmc.2009.07.044
PII: S0968-0896(09)00703-2
Knihovny.cz E-resources
- MeSH
- Antimalarials chemical synthesis chemistry pharmacology MeSH
- Enzyme Inhibitors chemical synthesis chemistry pharmacology MeSH
- Catalytic Domain MeSH
- Humans MeSH
- Organophosphonates chemistry MeSH
- Pentosyltransferases antagonists & inhibitors metabolism MeSH
- Plasmodium falciparum enzymology MeSH
- Computer Simulation MeSH
- Purines chemical synthesis chemistry pharmacology MeSH
- Drug Design MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antimalarials MeSH
- hypoxanthine-guanine-xanthine phosphoribosyltransferase MeSH Browser
- Enzyme Inhibitors MeSH
- Organophosphonates MeSH
- Pentosyltransferases MeSH
- Purines MeSH
The malarial parasite Plasmodium falciparum (Pf) lacks the de novo pathway and relies on the salvage enzyme, hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT), for the synthesis of the 6-oxopurine nucleoside monophosphates. Specific acyclic nucleoside phosphonates (ANPs) inhibit PfHGXPRT and possess anti-plasmodial activity. Two series of novel branched ANPs derived from 9-[2-(2-phosphonoethoxy)ethyl]purines were synthesized to investigate their inhibition of PfHGXPRT and human HGPRT. The best inhibitor of PfHGXPRT has a K(i) of 1 microM. The data showed that both the position and nature of the hydrophobic substituent change the potency and selectivity of the ANPs.
References provided by Crossref.org
A novel type of acyclic nucleoside phosphonates derived from 2-(phosphonomethoxy)propanoic acid
