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Antimalarial activity of N6-substituted adenosine derivatives.: Part 3

被引：30
作者：
Herforth, C
Wiesner, J
Heidler, P
Sanderbrand, S
Van Calenbergh, S
Jomaa, H
Link, A
机构：
[1] Univ Marburg, Inst Pharmaceut Chem, D-35032 Marburg, Germany
[2] Univ Hamburg, Abt Pharmazeut Chem, Inst Pharm, D-20146 Hamburg, Germany
[3] Univ Giessen, Inst Biochem, D-35392 Giessen, Germany
[4] Univ Ghent, Med Chem Lab, B-9000 Ghent, Belgium
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 04期
关键词：
D O I：
10.1016/j.bmc.2003.11.008
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：
A series of novel 3'-amido-3'-deoxy-N-6-(l-naphthylmethyl)adenosines was synthesized applying a polymer-assisted solution phase (PASP) protocol and was tested for anti-malarial activity versus the Dd2 strain of Plasm odium falciparum. Further, this series and 62 adenosine derivatives were analyzed regarding 1-deoxy-D-xylulose 5-phospate (DOXP) reductoisomerase inhibition. Biological evaluations revealed that the investigated 3,N-6-disubstituted adenosine derivatives displayed moderate but significant activity against the P. falciparum parasite in the low-micromolar range. On the molecular level, DOXP reductoisomerase utilizing an adenosyl-containing substrate was identified as a promising metabolic target for ligands of adenosine binding motifs. (C) 2003 Elsevier Ltd. All rights reserved.
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页码：755 / 762
页数：8
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