title: 5-Benzylidenethiazolidin-4-ones as multitarget inhibitors of bacterial Mur ligases.
abstract: Mur ligases participate in the intracellular path of bacterial peptidoglycan biosynthesis and constitute attractive, although so far underexploited, targets for antibacterial drug discovery. A series of hydroxy-substituted 5-benzylidenethiazolidin-4-ones were synthesized and tested as inhibitors of Mur ligases. The most potent compound 5 a was active against MurD-F with IC(50) values between 2 and 6 microm, making it a promising multitarget inhibitor of Mur ligases. Antibacterial activity against different strains, inhibitory activity against protein kinases, mutagenicity and genotoxicity of 5 a were also investigated, and kinetic and NMR studies were conducted.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Askerceva 7, 1000 Ljubljana, Slovenia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomasić
authors.forename: Nace
authors.initials: N
authors.lastname: Zidar
authors.forename: Andreja
authors.initials: A
authors.lastname: Kovac
authors.forename: Samo
authors.initials: S
authors.lastname: Turk
authors.forename: Mihael
authors.initials: M
authors.lastname: Simcic
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Manica
authors.initials: M
authors.lastname: Müller-Premru
authors.forename: Metka
authors.initials: M
authors.lastname: Filipic
authors.forename: Simona Golic
authors.initials: SG
authors.lastname: Grdadolnik
authors.forename: Anamarija
authors.initials: A
authors.lastname: Zega
authors.forename: Marko
authors.initials: M
authors.lastname: Anderluh
authors.forename: Stanislav
authors.initials: S
authors.lastname: Gobec
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
authors.forename: Lucija
authors.initials: L
authors.lastname: Peterlin Masic
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020552:Comet Assay; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010453:Peptide Synthases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; D010453:Peptide Synthases; C053379:UDP-N-acetylmuramoylalanine-D-glutamate ligase