Article (Scientific journals)
Exploration of the chemical space of novel naphthalene-sulfonamide and anthranilic acid-based inhibitors of penicillin-binding Proteins
Sosic, Izidor; Turk, Samo; Sinreih, Masa et al.
2012In Acta Chimica Slovenica, 59 (2), p. 380-388
Peer Reviewed verified by ORBi
 

Files


Full Text
Sosic 2012.pdf
Publisher postprint (489.1 kB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
naphthalene-sulfonamide; anthranilic acid; Penicillin-Binding Proteins; penicillin-resistance; noncovalent inhibitors
Abstract :
[en] Penicillin-binding proteins are a well established, validated and still a very promising target for the design and development of new antibacterial agents. Based on our previous discovery of several noncovalent small-molecule inhibitor hits for resistant PBPs we decided to additionally explore the chemical space around these compounds. In order to clarify their structure-activity relationships for PBP inhibition two new series of compounds were synthesized, characterized and evaluated biochemically: the derivatives of anthranilic acid and naphthalene-sulfonamide derivatives. The target compounds were tested for their inhibitory activities on three different transpeptidases: PBP2a from methicillin-resistant Staphylococcus aureus (MRSA) strains, PBP5fm from Enterococcus faecium strains, and PBP1b from Streptococcus pneumoniae strains. The most promising results for both of these series of compounds were obtained against the PBP2a enzyme with the IC50 values in the micromolar range. Although these results do not represent a significant breakthrough in the field of noncovalent PBP inhibitors, they do provide useful structure-activity relationship data, and thus a more solid basis for the design of potent and noncovalent inhibitors of resistant PBPs.
Research center :
GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège
CIP - Centre d'Ingénierie des Protéines - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Chemistry
Author, co-author :
Sosic, Izidor;  University of Ljubljana > Faculty of Pharmacy
Turk, Samo;  University of Ljubljana > Faculty of Pharmacy
Sinreih, Masa;  University of Ljubljana > Faculty of Pharmacy
Trost, Nusa;  University of Ljubljana > Faculty of Pharmacy
Verlaine, Olivier ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Amoroso, Ana Maria ;  Université de Liège - ULiège > Centre d'ingénierie des protéines
Zervosen, Astrid ;  Université de Liège - ULiège > Centre de recherches du cyclotron
Luxen, André ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse
Joris, Bernard ;  Université de Liège - ULiège > Département des sciences de la vie > Physiologie et génétique bactériennes
Gobec, Stanislav;  University of Ljubljana > Faculty of Pharmacy
Language :
English
Title :
Exploration of the chemical space of novel naphthalene-sulfonamide and anthranilic acid-based inhibitors of penicillin-binding Proteins
Publication date :
2012
Journal title :
Acta Chimica Slovenica
ISSN :
1318-0207
eISSN :
1580-3155
Publisher :
Slovenian Chemical Society
Volume :
59
Issue :
2
Pages :
380-388
Peer reviewed :
Peer Reviewed verified by ORBi
Name of the research project :
Eur-Intafar
Available on ORBi :
since 21 June 2012

Statistics


Number of views
146 (5 by ULiège)
Number of downloads
3 (1 by ULiège)

Scopus citations®
 
7
Scopus citations®
without self-citations
5

Bibliography


Similar publications



Contact ORBi