Author/Authors :
Francis Arhin، نويسنده , , Odette Bélanger، نويسنده , , Stéphane Ciblat، نويسنده , , Mohammed Dehbi، نويسنده , , Daniel Delorme، نويسنده , , Evelyne Dietrich، نويسنده , , Dilip Dixit، نويسنده , , Yanick Lafontaine، نويسنده , , Dario Lehoux، نويسنده , , Jing Liu، نويسنده , , Geoffrey A. McKay، نويسنده , , Greg Moeck، نويسنده , , S. Ranga Reddy and P. Manikyamba، نويسنده , , Yannick Rose، نويسنده , , Ramakrishnan Srikumar، نويسنده , , Kelly S.E. Tanaka، نويسنده , , Daniel M. Williams، نويسنده , , Philippe Gros، نويسنده , , Jerry Pelletier، نويسنده , , Thomas R. Parr Jr، نويسنده , , et al.، نويسنده ,
Abstract :
The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase.
Keywords :
2-Ureidothiophene-3-carboxylates , RNA polymerase , Reverse chemical genetics , Antibacterial agents
