学术探索
学术期刊
新闻热点
数据分析
智能评审

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.
引用
收藏
页码：755 / 762
页数：8
相关论文
共 26 条
[11]   Malaria in 2002 [J].
Greenwood, B ;
Mutabingwa, T .
NATURE, 2002, 415 (6872) :670-672
[12]   An improved approach to the synthesis of adenosine-5'-N-ethyluronamides of interest as adenosine receptor agonists [J].
Ha, SB ;
Nair, V .
TETRAHEDRON LETTERS, 1996, 37 (10) :1567-1570
[13]   Antimalarial activity of N6-substituted adenosine derivatives (Part 2) [J].
Herforth, C ;
Wiesner, J ;
Franke, S ;
Golisade, A ;
Jomaa, H ;
Link, A .
JOURNAL OF COMBINATORIAL CHEMISTRY, 2002, 4 (04) :302-314
[14]  
IKEHARA M, 1978, CHEM PHARM BULL, V26, P985
[15]   Vγ9/Vδ2 T cell activation induced by bacterial low molecular mass compounds depends on the 1-deoxy-D-xylulose 5-phosphate pathway of isoprenoid biosynthesis [J].
Jomaa, H ;
Feurle, J ;
Lühs, K ;
Kunzmann, V ;
Tony, HP ;
Herderich, M ;
Wilhelm, M .
FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 1999, 25 (04) :371-378
[16]   Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs [J].
Jomaa, H ;
Wiesner, J ;
Sanderbrand, S ;
Altincicek, B ;
Weidemeyer, C ;
Hintz, M ;
Türbachova, I ;
Eberl, M ;
Zeidler, J ;
Lichtenthaler, HK ;
Soldati, D ;
Beck, E .
SCIENCE, 1999, 285 (5433) :1573-1576
[17]   Adenosine receptors and their ligands [J].
Klotz, KN .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2000, 362 (4-5) :382-391
[18]   Bisubstrate inhibitors for the enzyme catechol-O-methyltransferase (COMT):: influence of inhibitor preorganisation and linker length between the two substrate moieties on binding affinity [J].
Lerner, C ;
Masjost, B ;
Ruf, A ;
Gramlich, V ;
Jakob-Roetne, R ;
Zürcher, G ;
Borroni, E ;
Diederich, F .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2003, 1 (01) :42-49
[19]  
Muller C E, 1993, Pharm Acta Helv, V68, P77, DOI 10.1016/0031-6865(93)90012-U
[20]  
OLAH ME, 1995, ANNU REV PHARMACOL, V35, P581, DOI 10.1146/annurev.pa.35.040195.003053
123