Document Detail

Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding Proteins of classes A, B and C.
MedLine Citation:
PMID:  22579615     Owner:  NLM     Status:  Publisher    
In response to the widespread use of β-lactam antibiotics bacteria have evolved drug resistance mechanisms that include the production of resistant Penicillin Binding Proteins (PBPs). Boronic acids are potent β-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): 1.3μM). 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)=26μM), a class B PBP (PBP2xR6 from Streptococcus pneumoniae, IC(50)=138μM) and a class C PBP (R39 from Actinomadura sp., IC(50)=0.6μM). This work opens new avenues towards the development of molecules that inhibit PBPs, and eventually display bactericidal effects, on distinct bacterial species.
Astrid Zervosen; André Bouillez; Alexandre Herman; Ana Amoroso; Bernard Joris; Eric Sauvage; Paulette Charlier; André Luxen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-16
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  -     ISSN:  1464-3391     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-5-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Centre de Recherches du Cyclotron, B30, Université de Liège, Sart-Tilman, B-4000 Liège, Belgium.
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