2-aminotetralones: Novel inhibitors of MurA and MurZ

被引：32

作者：

Dunsmore, Colin J. ^{[1
,2
]}

Miller, Keith ^{[2
,3
]}

Blake, Katy L. ^{[2
,3
]}

Patching, Simon G. ^{[2
]}

Henderson, Peter J. F. ^{[2
,4
]}

Garnett, James A. ^{[2
,3
]}

Stubbings, William J. ^{[2
,3
]}

Phillips, Simon E. V. ^{[2
,3
]}

Palestrant, Deborah J. ^{[5
]}

Angeles, Joseph De Los ^{[5
]}

Leeds, Jennifer A. ^{[6
]}

Chopra, Ian ^{[2
,3
]}

Fishwick, Colin W. G. ^{[1
,2
]}

机构：

[1] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England

[2] Univ Leeds, Antimicrobial Res Ctr, Leeds LS2 9JT, W Yorkshire, England

[3] Univ Leeds, Inst Mol & Cellular Biol, Leeds LS2 9JT, W Yorkshire, England

[4] Univ Leeds, Inst Membrane & Syst Biol, Leeds LS2 9JT, W Yorkshire, England

[5] Novartis Inst Biomed Res, Prot Struct Grp, Cambridge, MA 02139 USA

[6] Novartis Inst Biomed Res, Infect Dis Area, Cambridge, MA 02139 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 05期

关键词：

2-aminotetralone; MurA inhibitor; MurZ inhibitor; antibacterial activity;

D O I：

10.1016/j.bmcl.2008.01.089

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several 2-aminotetralones were identified as novel inhibitors of the bacterial enzymes MurA and MurZ. A number of these inhibitors demonstrated antibacterial activity against Staphylococcus aureus and Escherichia coli with MICs in the range 8-128 mu g/ml. Based on structure-activity relationships we propose that the alpha-aminoketone functionality is responsible for the inhibitory activity and evidence is provided to support a covalent mode of action involving the C115 thiol group of MurA/MurZ. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1730 / 1734

页数：5

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