Details

Autor(en) / Beteiligte

• Hocková, Dana
• Holý, Antonín
• Masojídková, Milena
• Keough, Dianne T.
• Jersey, John de
• Guddat, Luke W.

Titel

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

Ist Teil von

• Bioorganic & medicinal chemistry, 2009-09, Vol.17 (17), p.6218-6232

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 μM. The data showed that both the position and nature of the hydrophobic substituent change the potency and selectivity of the ANPs.