Tethered thiazolidinone dimers as inhibitors of the bacterial type III secretion system
- Resource Type
- Authors
- H.V. Nguyen; Heather B. Felise; Stona R. Jackson; Toni Kline; Samuel I. Miller; Kathleen C. Barry
- Source
- Bioorganic & Medicinal Chemistry Letters. 19:1340-1343
- Subject
- Secretory Pathway
Virulence
Chemistry
Stereochemistry
Escherichia coli Proteins
Dimer
Organic Chemistry
Clinical Biochemistry
Pharmaceutical Science
Biochemistry
Small molecule
Article
Anti-Bacterial Agents
Protein–protein interaction
Type three secretion system
chemistry.chemical_compound
Monomer
Drug Discovery
Type III Secretion Systems
Molecular Medicine
Thiazolidinediones
Secretion
Molecular Biology
Secretory pathway
- Language
- ISSN
- 0960-894X
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.