title: Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli.
abstract: Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic Escherichia coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here, we present the synthesis and biological evaluation of carboxylic acid isosteres, including, for example, tetrazoles, acyl sulfonamides, and hydroxamic acids of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli.
authors.affiliation: Department of Chemistry, Umeå University, SE-90187 Umeå, Sweden.
authors.forename: Veronica
authors.initials: V
authors.lastname: Berg
authors.forename: Pralay
authors.initials: P
authors.lastname: Das
authors.forename: Erik
authors.initials: E
authors.lastname: Chorell
authors.forename: Mattias
authors.initials: M
authors.lastname: Hedenström
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Pinkner
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hultgren
authors.forename: Fredrik
authors.initials: F
authors.lastname: Almqvist
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D010861:Fimbriae, Bacterial / Q000187:drug effects* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011728:Pyridones / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D011728:Pyridones; C017679:2-hydroxypyridine