Antibacterial chalcones––bioisosteric replacement of the 4′-hydroxy group Original Research Article

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)-].