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Bioorg Med Chem. 2006 Sep 1;14(17):5812-32. Epub 2006 Jun 8.

A new class of small molecule RNA polymerase inhibitors with activity against rifampicin-resistant Staphylococcus aureus.

Author information

1
Targanta Therapeutics Inc, 7170 Frederick Banting, 2nd Floor, St. Laurent, Que., Canada H4S 2A1.

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.

PMID:
16759869
DOI:
10.1016/j.bmc.2006.05.035
[Indexed for MEDLINE]

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