Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system.

Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.65). 02/2009; 19(5):1340-3. DOI: 10.1016/j.bmcl.2009.01.047
Source: PubMed

ABSTRACT 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.

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