Article (Scientific journals)
Synthesis and Evaluation of 3-(Dihydroxyboryl)benzoic Acids as d,d-Carboxypeptidase R39 Inhibitors.
Inglis, Steven R.; Zervosen, Astrid; Woon, Esther C.Y. et al.
2009In Journal of Medicinal Chemistry
Peer Reviewed verified by ORBi
 

Files


Full Text
jm9009718.pdf
Publisher postprint (1.04 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Penicillin-binding protein; boronic acid; peptidoglycan
Abstract :
[en] Penicillin binding proteins (PBPs) catalyze steps in the biosynthesis of bacterial cell walls and are the targets for the beta-lactam antibiotics. Non-beta-lactam based antibiotics that target PBPs are of interest because bacteria have evolved resistance to the beta-lactam antibiotics. Boronic acids have been developed as inhibitors of the mechanistically related serine beta-lactamases and serine proteases; however, they have not been explored extensively as PBP inhibitors. Here we report aromatic boronic acid inhibitors of the d,d-carboxypeptidase R39 from Actinomadura sp. strain. Analogues of an initially identified inhibitor [3-(dihydroxyboryl)benzoic acid 1, IC(50) 400 muM] were prepared via routes involving pinacol boronate esters, which were deprotected via a two-stage procedure involving intermediate trifluorborate salts that were hydrolyzed to provide the free boronic acids. 3-(Dihydroxyboryl)benzoic acid analogues containing an amide substituent in the meta, but not ortho position were up to 17-fold more potent inhibitors of the R39 PBP and displayed some activity against other PBPs. These compounds may be useful for the development of even more potent boronic acid based PBP inhibitors with a broad spectrum of antibacterial activity.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
CIP - Centre d'Ingénierie des Protéines - ULiège
Disciplines :
Chemistry
Biochemistry, biophysics & molecular biology
Immunology & infectious disease
Author, co-author :
Inglis, Steven R.
Zervosen, Astrid ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Woon, Esther C.Y.
Gerards, Thomas ;  Université de Liège - ULiège > Département des sciences de la vie > Biochimie végétale
Teller, Nathalie
Fischer S, Delphine
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron
Schofield, Christopher J.
Language :
English
Title :
Synthesis and Evaluation of 3-(Dihydroxyboryl)benzoic Acids as d,d-Carboxypeptidase R39 Inhibitors.
Publication date :
04 September 2009
Journal title :
Journal of Medicinal Chemistry
ISSN :
0022-2623
eISSN :
1520-4804
Publisher :
American Chemical Society, Washington, United States - District of Columbia
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
EUR-INTAFAR
Available on ORBi :
since 28 September 2009

Statistics


Number of views
111 (23 by ULiège)
Number of downloads
7 (6 by ULiège)

Scopus citations®
 
36
Scopus citations®
without self-citations
27
OpenCitations
 
37

Bibliography


Similar publications



Contact ORBi