Constituents with potent α-glucosidase inhibitory activity from Pueraria lobata (Willd.) ohwi

Bioorg Med Chem Lett. 2017 May 1;27(9):1993-1998. doi: 10.1016/j.bmcl.2017.03.013. Epub 2017 Mar 7.

Abstract

One new flavone hydrate named lobatflavate (1), one new chromone named lobatchrosin (2), and one new isoflavone named 3S,4R-tuberosin (3), along with four known isoflavone analogues (4-7), were isolated from the traditional Chinese medicinal plant of Pueraria lobata (Willd.) ohwi. Their structures were elucidated by extensive spectroscopic methods of IR, UV, HR-ESI-MS, 1D and 2D NMR. The absolute configuration of 3 was determined by CD spectrum associated with TD-DFT calculation analysis. All compounds except for 2 were assayed the inhibitory activity against α-glucosidase. Every tested compound was proved to be more active than positive control of acarbose. Of which 1 and 4 showed significant activity with IC50 value of 1.79μM and 23.01μM (IC50 of acarbose was 1998.79μM). Enzyme kinetic experiments revealed that 1 was irreversible whereas 4 was reversible and non-competitive α-glucosidase inhibitors. Moreover, structure-activity relationship was discussed and the docking studies of 1, 3 and 4 were also carried out.

Keywords: Chromone; Flavones; Isoflavones; Pueraria lobata (Willd.) ohwi.; α-Glucosidase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromones / chemistry
  • Chromones / pharmacology
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacology*
  • Flavones / chemistry
  • Flavones / pharmacology
  • Glycoside Hydrolase Inhibitors / chemistry*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology
  • Isoflavones / chemistry
  • Isoflavones / pharmacology
  • Molecular Docking Simulation
  • Pueraria / chemistry*
  • Structure-Activity Relationship
  • alpha-Glucosidases / metabolism

Substances

  • Chromones
  • Drugs, Chinese Herbal
  • Flavones
  • Glycoside Hydrolase Inhibitors
  • Hypoglycemic Agents
  • Isoflavones
  • alpha-Glucosidases