Aminocarboxylic acids related to aspergillomarasmine A (AMA) and ethylenediamine-N,N′-disuccinic acid (EDDS) are strong zinc-binders and inhibitors of the metallo-beta-lactamase NDM-1

被引：17

作者：

Tehrani, Kamaleddin H. M. E. ^{[1
]}

Fu, Haigen ^{[2
]}

Bruchle, Nora C. ^{[1
]}

Mashayekhi, Vida ^{[3
]}

Lujan, Alejandro Prats ^{[2
]}

van Haren, Matthijs J. ^{[1
]}

Poetarends, Gerrit J. ^{[2
]}

Martin, Nathaniel, I ^{[1
]}

机构：

[1] Leiden Univ, Inst Biol Leiden, Biol Chem Grp, Sylviusweg 72, NL-2333 BE Leiden, Netherlands

[2] Univ Groningen, Dept Chem & Pharmaceut Biol, Antonius Deusinglaan 1, NL-9713 AV Groningen, Netherlands

[3] Univ Utrecht, Fac Sci, Dept Biol, Div Cell Biol, Utrecht, Netherlands

来源：

CHEMICAL COMMUNICATIONS | 2020年 / 56卷 / 20期

基金：

欧洲研究理事会;

关键词：

ASYMMETRIC-SYNTHESIS;

D O I：

10.1039/d0cc00356e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A series of aminocarboxylic acid analogues of aspergillomarasmine A (AMA) and ethylenediamine-N,N'-disuccinic acid (EDDS) were chemoenzymatically synthesized via the addition of various mono- and diamine substrates to fumaric acid catalyzed by the enzyme EDDS lyase. Many of these novel AMA and EDDS analogues demonstrate potent inhibition of the bacterial metallo-beta-lactamase NDM-1. Isothermal titration calorimetry assays revealed a strong correlation between the inhibitory potency of the compounds and their ability to bind zinc. Compounds 1a (AMA), 1b (AMB), 5 (EDDS), followed by 1d and 8a, demonstrate the highest synergy with meropenem resensitizing an NDM-1 producing strain of E. coli to this important carbapenem of last resort.

引用

页码：3047 / 3049

页数：3