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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Anti-Bacterial Agents / chemical synthesis
-
Anti-Bacterial Agents / chemistry*
-
Anti-Bacterial Agents / pharmacology
-
Bacterial Proteins / antagonists & inhibitors*
-
Bacterial Proteins / metabolism
-
Comet Assay
-
Enzyme Inhibitors / chemical synthesis
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology
-
Kinetics
-
Magnetic Resonance Spectroscopy
-
Microbial Sensitivity Tests
-
Peptide Synthases / antagonists & inhibitors
-
Peptide Synthases / metabolism
-
Structure-Activity Relationship
-
Thiazolidinediones / chemical synthesis
-
Thiazolidinediones / chemistry*
-
Thiazolidinediones / pharmacology
Substances
-
Anti-Bacterial Agents
-
Bacterial Proteins
-
Enzyme Inhibitors
-
Thiazolidinediones
-
Peptide Synthases
-
UDP-N-acetylmuramoylalanine-D-glutamate ligase