title: Dual Inhibitor of MurD and MurE Ligases from Escherichia coli and Staphylococcus aureus.
abstract: MurD and MurE ligases, consecutive enzymes participating in the intracellular steps of bacterial peptidoglycan biosynthesis, are important targets for antibacterial drug discovery. We have designed, synthesized, and evaluated the first d-glutamic acid-containing dual inhibitor of MurD and MurE ligases from Escherichia coli and Staphylococcus aureus (IC50 values between 6.4 and 180 μM) possessing antibacterial activity against Gram-positive S. aureus and its methicillin-resistant strain (MRSA) with minimal inhibitory concentration (MIC) values of 8 μg/mL. The inhibitor was also found to be noncytotoxic for human HepG2 cells at concentrations below 200 μM.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomašić
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Roman
authors.initials: R
authors.lastname: Sink
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Nace
authors.initials: N
authors.lastname: Zidar
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Anja
authors.initials: A
authors.lastname: Fic
authors.affiliation: Institut de Biologie Structurale, Bacterial Pathogenesis Group, Université Grenoble I , 38027 Grenoble, France ; Commissariat à l'Energie Atomique (CEA) , IBS, 38027 Grenoble, France ; Centre National de la Recherche Scientifique (CNRS) , IBS, 41 rue Jules Horowitz, 38027 Grenoble, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Contreras-Martel
authors.affiliation: Institut de Biologie Structurale, Bacterial Pathogenesis Group, Université Grenoble I , 38027 Grenoble, France ; Commissariat à l'Energie Atomique (CEA) , IBS, 38027 Grenoble, France ; Centre National de la Recherche Scientifique (CNRS) , IBS, 41 rue Jules Horowitz, 38027 Grenoble, France.
authors.forename: Andréa
authors.initials: A
authors.lastname: Dessen
authors.affiliation: Univ Paris-Sud , Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR 8619, 91405 Orsay, France ; CNRS , 91405 Orsay, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Patin
authors.affiliation: Univ Paris-Sud , Laboratoire des Enveloppes Bactériennes et Antibiotiques, Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR 8619, 91405 Orsay, France ; CNRS , 91405 Orsay, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.affiliation: Institute of Microbiology and Immunology, Medical Faculty, University of Ljubljana , 1105 Ljubljana, Slovenia.
authors.forename: Manica
authors.initials: M
authors.lastname: Müller-Premru
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Anamarija
authors.initials: A
authors.lastname: Zega
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.affiliation: Faculty of Pharmacy, University of Ljubljana , Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
keywords: 2-thioxothiazolidin-4-one; Mur ligase; antibacterial agent; inhibitor; peptidoglycan