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

Hockova, Dana, Holy, Antonín, Masojidkova, Milena, Keough, Dianne T., de Jersey, John and Guddat, Luke W. (2009) 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. Bioorganic & Medicinal Chemistry, 17 17: 6218-6232. doi:10.1016/j.bmc.2009.07.044


Author Hockova, Dana
Holy, Antonín
Masojidkova, Milena
Keough, Dianne T.
de Jersey, John
Guddat, Luke W.
Title 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
Formatted title
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
Journal name Bioorganic & Medicinal Chemistry   Check publisher's open access policy
ISSN 0968-0896
Publication date 2009-07-25
Sub-type Article (original research)
DOI 10.1016/j.bmc.2009.07.044
Open Access Status Not Open Access
Volume 17
Issue 17
Start page 6218
End page 6232
Total pages 15
Editor Dr. Chi-Huey Wong
H Waldmann
Yuichi Hashimoto
Place of publication United Kingdom
Publisher Pergamon
Language eng
Subject C1
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
920109 Infectious Diseases
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 Ki of 1 μM. The data showed that both the position and nature of the hydrophobic substituent change the potency and selectivity of the ANPs.
Keyword Acyclic nucleoside phosphonates
Malaria parasite
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 03 Sep 2009, 17:42:57 EST by Mr Andrew Martlew on behalf of School of Chemistry & Molecular Biosciences