Design and synthesis of C-2 substituted Thiazolo and Dihydrothiazolo ring-fused 2-Pyridones: Pilicides with increased antivirulence activity
Chorell, E. and Pinkner, J.S. and Phan, Gilles and Edvinsson, S. and Buelens, Floris and Remaut, Han and Waksman, Gabriel and Hultgren, S.J. and Almqvist, F. (2010) Design and synthesis of C-2 substituted Thiazolo and Dihydrothiazolo ring-fused 2-Pyridones: Pilicides with increased antivirulence activity. Journal of Medicinal Chemistry 53 (15), pp. 5690-5695. ISSN 0022-2623.
Pilicides block pili formation by binding to pilus chaperones and blocking their function in the chaperone/usher pathway in E. coli. Various C-2 substituents were introduced on the pilicide scaffold by design and synthetic method developments. Experimental evaluation showed that proper substitution of this position affected the biological activity of the compound. Aryl substituents resulted in pilicides with significantly increased potencies as measured in pill-dependent biofilm and hemagglutination assays. The structural basis of the PapD chaperone-pilicide interactions was determined by X-ray crystallography.
|Keyword(s) / Subject(s):||Uropathogenic Escherichia-Coli, inhibit pilus biogenesis, Chaperone-Usher Pathway, bicyclic 2-Pyridones, targeting virulence, fiber formation, outer-membrane, functionalization, bacteria, biology|
|School:||Birkbeck Schools and Departments > School of Science > Biological Sciences|
|Research Centre:||Structural Molecular Biology, Institute of (ISMB)|
|Date Deposited:||21 Feb 2011 11:19|
|Last Modified:||06 Dec 2016 10:46|
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