Synthesis and Biological Evaluation of Bicyclic ?-Lactams and 2-Pyridinones : Pilicides Targeting Pilus Biogenesis in Pathogenic Bacteria
New methods have been developed for the synthesis of bicyclic ?-lactams and 2-pyridinones by combining acyl Meldrum’s acids and ?2-thiazolines. The 2-pyridinones were synthesised both in solution using conventional heating or microwave assisted heating as well as by solid supported chemistry.The compounds (pilicides) were designed to interfere with the assembly of pili in uropathogenic E. coli by inhibiting the periplasmic chaperones. The affinity of the pilicides to the chaperones was investigated with surface plasmon resonance technique (Biacore) and with relaxation-edited 1H NMR spectroscopy experiments. Finally, the pilicides were investigated for their ability to inhibit pili formation in uropathogenic E. coli in a hemagglutination assay, where members of the 2-pyridinone family proved to be able to cause depiliation.
Source Type:Doctoral Dissertation
Keywords:NATURAL SCIENCES; Chemistry; Organic chemistry; Organic chemistry; ?-lactam; 2-pyridinone; 2-pyridone; Meldrum’s acid; ?2-thiazoline; solid-phase synthesis; microwave assisted synthesis; antibacterial; pili; pilicide; Organisk kemi; Organic Chemistry; organisk kemi
Date of Publication:01/01/2003