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

Bioorg Med Chem Lett. 2023 May 15:88:129302. doi: 10.1016/j.bmcl.2023.129302. Epub 2023 Apr 22.

Abstract

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 IC50 values of 0.7 ± 0.1 and 2.3 ± 0.3 μM, 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.

Keywords: Coumarin oligomer; Enzymatic transformation; Kinetic analysis; Polyphenol oxidase; α-Glucosidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycoside Hydrolase Inhibitors* / chemistry
  • Glycoside Hydrolase Inhibitors* / pharmacology
  • Kinetics
  • Umbelliferones* / pharmacology
  • alpha-Glucosidases / metabolism

Substances

  • Glycoside Hydrolase Inhibitors
  • esculetin
  • Umbelliferones
  • alpha-Glucosidases