期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 19, 期 5, 页码 1340-1343出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.01.047
关键词
Type III Secretion; Thiazolidinone; Bacterial virulence; Antibiotic; Protein-protein interaction
资金
- NIAID [U54 A105714]
Disruption of protein-protein interactions by small molecules is achievable but presents significant hurdles for effective compound design. In earlier work we identified a series of thiazolidinone inhibitors of the bacterial type III secretion system (T3SS) and demonstrated that this scaffold had the potential to be expanded into molecules with broad-spectrum anti-Gram negative activity. We now report on one series of thiazolidinone analogs in which the heterocycle is presented as a dimer at the termini of a series of linkers. Many of these dimers inhibited the T3SS-dependent secretion of a virulence protein at concentrations lower than that of the original monomeric compound identified in our screen. (C) 2009 Elsevier Ltd. All rights reserved.
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