Generation of xanthohumol derivatives through fungi-mediated biotransformation

Xanthohumol (XTH, 1), a major prenylated chalcone in hops, has attracted considerable interests because of its pharmaceutical potency. To explore more related derivatives of XTH, its biotransformation was performed using the in vitro microbial model. Fungus Mucor sp. exhibited a robust biocatalytic feature to transform the substrate. Preparative fungi-mediated biotransformation led to the isolation of two new (2 and 5) and eight known (3, 4 and 6-11) metabolites. The two new metabolites were identified as (2″R)-dihydroxanthohumol B (2) and xanthohumol L 4'-O-β-D-glucopyranoside (5) based on the combined spectroscopic analysis. According to the cytotoxic activities of all metabolites, compounds 7 and 9 showed relatively sensitive cytotoxic activity against A375 and A549 cancer cell lines, respectively. These findings not only provided a biological approach to achieve the derivatives of XTH but also gave an information for the lead optimisation of XTH for the development of potential anti-cancer agents.