Discovery of novel lipophilic inhibitors of OXA-10 enzyme (class D β-lactamase) by screening amino analogs and homologs of citrate and isocitrate
Discovery of novel lipophilic inhibitors of OXA-10 enzyme (class D β-lactamase) by screening amino analogs and homologs of citrate and isocitrate
复制标题
DOI：
10.1016/j.bmcl.2009.04.149
复制
发表时间：
2009-07-01
影响因子：
2.7
通讯作者：
Marchand-Brynaert, Jacqueline
中科院分区：
文献类型：
--
作者：
Beck, Josephine;Vercheval, Lionel;Marchand-Brynaert, Jacqueline
氨基柠檬酸酯（和同系物）衍生物是通过用溴乙酸酯（和丙烯酸乙酯）对甘氨酸席夫碱进行双烷基化，然后进行 N-酰化和酯（部分或完全）脱保护来制备的。类似地通过用富马酸二乙酯单烷基化获得氨基异柠檬酸酯。对代表性 β-内酰胺酶的评估表明，游离酸衍生物是 A 类酶的适度抑制剂，而它们的苄酯对 OXA-10（D 类酶）表现出良好的抑制作用。对接实验以活性位点的疏水相互作用为特征。 (C) 2009 Elsevier Ltd. 保留所有权利。
Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete) deprotection. Aminoisocitrate was similarly obtained by mono-alkylation with diethyl fumarate. Evaluation against representative beta-lactamases revealed that the free acid derivatives are modest inhibitors of class A enzymes, whilst their benzyl esters showed a good inhibition of OXA-10 (class D enzyme). A docking experiment featured hydrophobic interactions in the active site. (C) 2009 Elsevier Ltd. All rights reserved.