Enzymatic transformation of esculetin as a potent class of α-glucosidase inhibitors

A rapid and simple enzymatic transformation of the representative coumarin esculetin (1) with polyphenol oxidase originating from Agaricus bisporus afforded five new oxidized metabolites, esculetinins A (2), B (3), C (4), D (5), and E (6), together with the known compound isoeuphorbetin (7). The structures of the oligomerized transformation products were established on the basis of spectroscopic interpretations. The esculetin oligomers 2 and 3 revealed highly enhanced inhibitory activities against α-glucosidase, with IC values of 0.7 ± 0.1 and 2.3 ± 0.3μM, respectively, as compared to the original esculetin. Kinetic analysis also exhibited that the two new potent metabolites 2 and 3 have competitive modes of action.