Recent advances in structural modification and biological activities of isoliquiritigenin and liquiritigenin

Liquiritigenin and isoliquiritigenin, major bioactive flavonoids from licorice, exhibit promising pharmacological properties. However, their poor solubility, low oral bioavailability and weak metabolic stability limit their clinical application. Various site-specific structural modification strategies have been adopted by researchers to tackle these limitations. Functionalization with Mannich bases, prenyloxy groups, thiosemicarbazone moieties, halogens and glycosyl groups, as well as structural modifications via phosphorylation and acylation, can effectively tune their physicochemical properties, bioactivity, targeting ability and safety. These strategies support the rational design of potent flavonoid-derived drug candidates for clinical application.