Synthesis and biological evaluation of Bicyclic β-Lactams and 2-Pyridinones Pilicides Targeting Pilus Biogenesis in Pathogenic Bacteria

University dissertation from Umeå : Department of Chemistry, Organic Chemistry, Umeå University

Author: Hans Emtenäs; Umeå Universitet.; [2003]

Keywords: NATURVETENSKAP; NATURAL SCIENCES; Organic chemistry; β-lactam; 2-pyridinone; 2-pyridone; Meldrum’s acid; Δ2-thiazoline; solid-phase synthesis; microwave assisted synthesis; antibacterial; pili; pilicide; Organisk kemi; NATURAL SCIENCES Chemistry Organic chemistry; NATURVETENSKAP Kemi Organisk kemi; organisk kemi; Organic Chemistry;

Abstract: New methods have been developed for the synthesis of bicyclic β-lactams and 2-pyridinones by combining acyl Meldrum’s acids and Δ2-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.

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