Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase

被引：32

作者：

Clinch, Keith ^{[1
]}

Crump, Douglas R. ^{[1
]}

Evans, Gary B. ^{[1
]}

Hazleton, Keith Z. ^{[2
]}

Mason, Jennifer M. ^{[1
]}

Schramm, Vern L. ^{[2
]}

Tyler, Peter C. ^{[1
]}

机构：

[1] Ind Res Ltd, Carbohydrate Chem, Lower Hutt 5040, New Zealand

[2] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 17期

关键词：

Phosphoribosyltransferase; Malaria; HGXPRTase; Purine salvage; Protozoa; TRANSITION-STATE ANALOG; ANTI-PROTOZOAL AGENTS; NUCLEOSIDE PHOSPHONATES; PYRIMIDINE METABOLISM; POTENTIAL INHIBITORS; PURINE; PHOSPHORYLASE; PHOSPHOSERINE; MALARIA; ENZYMES;

D O I：

10.1016/j.bmc.2013.02.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：5629 / 5646

页数：18

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