Reference : Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins o...
Scientific journals : Article
Physical, chemical, mathematical & earth Sciences : Chemistry
http://hdl.handle.net/2268/125412
Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C.
English
Zervosen, Astrid mailto [Université de Liège - ULg > > Centre de recherches du cyclotron]
Bouillez, André mailto [Université de Liège - ULg > Département de chimie (sciences) > Département de chimie (sciences)]
Herman, Alexandre [> > > >]
Amoroso, Ana Maria mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines]
Joris, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > Physiologie et génétique bactériennes]
Sauvage, Eric mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines]
Charlier, Paulette mailto [Université de Liège - ULg > Département des sciences de la vie > Cristallographie des macromolécules biologiques]
Luxen, André mailto [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse]
2012
Bioorganic & Medicinal Chemistry
Elsevier Science
20
12
3915-24
Yes (verified by ORBi)
International
0968-0896
1464-3391
Oxford
United Kingdom
[en] In response to the widespread use of beta-lactam antibiotics bacteria have evolved drug resistance mechanisms that include the production of resistant Penicillin Binding Proteins (PBPs). Boronic acids are potent beta-lactamase inhibitors and have been shown to display some specificity for soluble transpeptidases and PBPs, but their potential as inhibitors of the latter enzymes is yet to be widely explored. Recently, a (2,6-dimethoxybenzamido)methylboronic acid was identified as being a potent inhibitor of Actinomadura sp. R39 transpeptidase (IC(50): 1.3muM). In this work, we synthesized and studied the potential of a number of acylaminomethylboronic acids as inhibitors of PBPs from different classes. Several derivatives inhibited PBPs of classes A, B and C from penicillin sensitive strains. The (2-nitrobenzamido)methylboronic acid was identified as a good inhibitor of a class A PBP (PBP1b from Streptococcus pneumoniae, IC(50)=26muM), a class B PBP (PBP2xR6 from Streptococcus pneumoniae, IC(50)=138muM) and a class C PBP (R39 from Actinomadura sp., IC(50)=0.6muM). This work opens new avenues towards the development of molecules that inhibit PBPs, and eventually display bactericidal effects, on distinct bacterial species.
http://hdl.handle.net/2268/125412
10.1016/j.bmc.2012.04.018
Copyright (c) 2012 Elsevier Ltd. All rights reserved.

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