PMID- 22579615
OWN - NLM
STAT- In-Data-Review
DA  - 20120529
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 20
IP  - 12
DP  - 2012 Jun 15
TI  - Synthesis and evaluation of boronic acids as inhibitors of Penicillin Binding
      Proteins of classes A, B and C.
PG  - 3915-24
AB  - 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.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
AD  - Centre de Recherches du Cyclotron, B30, Universite de Liege, Sart-Tilman, B-4000 
      Liege, Belgium.
FAU - Zervosen, Astrid
AU  - Zervosen A
FAU - Bouillez, Andre
AU  - Bouillez A
FAU - Herman, Alexandre
AU  - Herman A
FAU - Amoroso, Ana
AU  - Amoroso A
FAU - Joris, Bernard
AU  - Joris B
FAU - Sauvage, Eric
AU  - Sauvage E
FAU - Charlier, Paulette
AU  - Charlier P
FAU - Luxen, Andre
AU  - Luxen A
LA  - eng
PT  - Journal Article
DEP - 20120416
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
SB  - IM
EDAT- 2012/05/15 06:00
MHDA- 2012/05/15 06:00
CRDT- 2012/05/15 06:00
PHST- 2012/02/07 [received]
PHST- 2012/04/05 [revised]
PHST- 2012/04/07 [accepted]
PHST- 2012/04/16 [aheadofprint]
AID - S0968-0896(12)00293-3 [pii]
AID - 10.1016/j.bmc.2012.04.018 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2012 Jun 15;20(12):3915-24. Epub 2012 Apr 16.