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
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
19666228
DOI
10.1016/j.bmc.2009.07.044
PII: S0968-0896(09)00703-2
Knihovny.cz E-zdroje
- MeSH
- antimalarika chemická syntéza chemie farmakologie MeSH
- inhibitory enzymů chemická syntéza chemie farmakologie MeSH
- katalytická doména MeSH
- lidé MeSH
- organofosfonáty chemie MeSH
- pentosyltransferasy antagonisté a inhibitory metabolismus MeSH
- Plasmodium falciparum enzymologie MeSH
- počítačová simulace MeSH
- puriny chemická syntéza chemie farmakologie MeSH
- racionální návrh léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antimalarika MeSH
- hypoxanthine-guanine-xanthine phosphoribosyltransferase MeSH Prohlížeč
- inhibitory enzymů MeSH
- organofosfonáty MeSH
- pentosyltransferasy MeSH
- puriny 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.
Citace poskytuje Crossref.org
A novel type of acyclic nucleoside phosphonates derived from 2-(phosphonomethoxy)propanoic acid
