Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli
نویسندگان
چکیده
منابع مشابه
C-Terminal properties are important for ring-fused 2-pyridones that interfere with the chaperone function in uropathogenic E. coli.
Virulence-associated organelles, termed pili or fimbriae, are assembled via the highly conserved chaperone-usher pathway in a vast number of pathogenic bacteria. Substituted bicyclic 2-pyridones, pilicides, inhibit pilus formation, possibly by interfering with the active site residues Arg8 and Lys112 of chaperones in uropathogenic E. coli. In this article we describe the synthesis and evaluatio...
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A new method for the solid-phase synthesis of enantiomerically enriched highly substituted ring-fused 2-pyridinones 13 has been developed. The synthesis mediates introduction of substituents at two positions in the 2-pyridinone ring in a diverse manner and is suitable for parallel synthesis. (19)F NMR spectroscopy was used as a tool to monitor each of the five steps in the reaction sequence. Th...
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The replacement of a carboxylic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry. The general underlying principle is that by maintaining the features of the carboxylic acid critical for biological activity, but appropriately modifying the physicochemical properties, improved analogs may result. In this context, a systematic assessment of the ph...
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Substituted thiazolo ring-fused 2-pyridones, called pilicides, possess novel antibacterial properties and inhibit pilus assembly in Uropathogenic Escherichia coli. Recently, a small number of oxygen analogues of active pilicides have shown maintained ability to disrupt pilus assembly. Here an improved methodology for the synthesis of oxazolo ring-fused 2pyridones is presented, allowing dihydro ...
متن کاملRationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria.
A chemical synthesis platform with broad applications and flexibility was rationally designed to inhibit biogenesis of adhesive pili assembled by the chaperone-usher pathway in Gram-negative pathogens. The activity of a family of bicyclic 2-pyridones, termed pilicides, was evaluated in two different pilus biogenesis systems in uropathogenic Escherichia coli. Hemagglutination mediated by either ...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 2008
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2008.05.020