title: Antibacterial chalcones--bioisosteric replacement of the 4'-hydroxy group.
abstract: Hydroxy chalcones, for example, Licochalcone A, has for several years been known to be antibacterial. The low aqueous solubility and the medium antibacterial potency have limited the usefulness of the compounds. We describe the bioisosteric replacement of the essential 4'-hydroxy group in the hydroxy chalcones with bioisosters of varied degrees of acidity resulting in both more potent and more soluble compounds. The more acidic 4'-hydroxy analogues (e.g., 3'-fluoro- or 3',5'-difluoro-) gave almost inactive compounds whereas exchanging the hydroxy group with a carboxy group resulted in a potent compound with a high aqueous solubility. Further optimisation and SAR-analysis resulted in soluble and potent carboxy chalcones [e.g., 3,5-dibromo- and 3,5-di(trifluoromethyl)-].
authors.affiliation: Lica Pharmaceuticals A/S, Fruebjergvej 3, DK-2100 Copenhagen, Denmark.
authors.forename: Simon Feldbaek
authors.initials: SF
authors.lastname: Nielsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Boesen
authors.forename: Mogens
authors.initials: M
authors.lastname: Larsen
authors.forename: Kristian
authors.initials: K
authors.lastname: Schønning
authors.forename: Hasse
authors.initials: H
authors.lastname: Kromann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006878:Hydroxides / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D047188:Chalcones; D006878:Hydroxides