A study of the effects of substituents on the selectivity of the binding of N-arylaminomethylene malonate inhibitors to DHODH

被引：18
作者：
Cowen, Deborah [1 ]
Bedingfield, Paul [2 ]
McConkey, Glenn A. [2 ]
Fishwick, Colin W. G. [1 ]
Johnson, A. Peter [1 ]
机构：
[1] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England
[2] Univ Leeds, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 03期
基金：
英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;
关键词：
DHODH; Plasmodium falciparum; Molecular modelling; FALCIPARUM DIHYDROOROTATE DEHYDROGENASE; PLASMODIUM-FALCIPARUM; KINETIC MECHANISM; AUTOMATED DOCKING; MALARIA; POTENT; IDENTIFICATION; DESIGN;
D O I：
10.1016/j.bmcl.2009.11.079
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of mono- and di-substituted N-arylaminomethylene malonates have been used to probe the potential of utilizing additional H-bonding contacts in the ubiquinone binding channel, for selective inhibition between either human or Plasmodium DHODH. Altered 'head' group functionalities have been utilized in order to probe the role of specific functionalities within the inhibitors in terms of enzyme affinity and selectivity. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1284 / 1287
页数：4
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