Enzymatic transformation products of phloretin as potent antiadipogenic compounds

Enzymatic structure modification of the representative chalcone phloretin (1) with polyphenol oxidase from Agaricus bisporus origin produced 2 new biphenyl-type phloreoxin (2) and phloreoxinone (3), and a previously undescribed (2R)-5,7,3',5'-tetrahydroxyflavanone (4). The structure of these new oxidized products 2-4 elucidated by interpreting the spectroscopic data (NMR and FABMS) containing the absolute stereochemistry is established by the analysis of the circular dichroism spectrum. Compared to the original phloretin, the new products (2) and (3) showed highly improved antiadipogenic potencies both toward pancreatic lipase and accumulation of 3T3-L1 cells. Also, phloreoxin (2) effectively inhibited the expression of C/EBPβ, PPARγ, and aP2 at the mRNA level in the 3T3 adipocytes. Thus, phloreoxin (2), containing a biphenyl moiety catalyzed by A. bisporus polyphenol oxidase, have the potential to influence the antiadipogenic capacity.