Reference : Exploration of the chemical space of novel naphthalene-sulfonamide and anthranilic acid-...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Physical, chemical, mathematical & earth Sciences : Chemistry
http://hdl.handle.net/2268/125751
Exploration of the chemical space of novel naphthalene-sulfonamide and anthranilic acid-based inhibitors of penicillin-binding Proteins
English
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 mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Amoroso, Ana Maria mailto [Université de Liège - ULg > > Centre d'ingénierie des protéines >]
Zervosen, Astrid mailto [Université de Liège - ULg > > Centre de recherches du cyclotron >]
Luxen, André mailto [Université de Liège - ULg > Département de chimie (sciences) > Chimie organique de synthèse >]
Joris, Bernard mailto [Université de Liège - ULg > Département des sciences de la vie > Physiologie et génétique bactériennes >]
Gobec, Stanislav [University of Ljubljana > Faculty of Pharmacy > > >]
2012
Acta Chimica Slovenica
Slovenian Chemical Society
59
2
380-388
Yes (verified by ORBi)
International
1318-0207
[en] naphthalene-sulfonamide ; anthranilic acid ; Penicillin-Binding Proteins ; penicillin-resistance ; noncovalent inhibitors
[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.
Centre de Recherches du Cyclotron - CRC ; Centre d'Ingénierie des Protéines - CIP
Eur-Intafar
Researchers ; Professionals
http://hdl.handle.net/2268/125751

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