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.
Bioorg Med Chem
; 17(17): 6218-32, 2009 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-19666228
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Pentosiltransferases
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Plasmodium falciparum
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Purinas
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Inibidores Enzimáticos
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Antimaláricos
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
República Tcheca