Article (Scientific journals)
Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C.
Zervosen, Astrid; Bouillez, André; Herman, Alexandre et al.
2012In Bioorganic and Medicinal Chemistry, 20 (12), p. 3915-24
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Abstract :
[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.
Disciplines :
Chemistry
Author, co-author :
Zervosen, Astrid ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Bouillez, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Département de chimie (sciences)
Herman, Alexandre
Amoroso, Ana Maria ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Joris, Bernard ;  Université de Liège - ULiège > Département des sciences de la vie > Physiologie et génétique bactériennes
Sauvage, Eric ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Charlier, Paulette ;  Université de Liège - ULiège > Département des sciences de la vie > Cristallographie des macromolécules biologiques
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Language :
English
Title :
Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C.
Publication date :
2012
Journal title :
Bioorganic and Medicinal Chemistry
ISSN :
0968-0896
eISSN :
1464-3391
Publisher :
Elsevier Science, Oxford, United Kingdom
Volume :
20
Issue :
12
Pages :
3915-24
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 Elsevier Ltd. All rights reserved.
Available on ORBi :
since 18 June 2012

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