Identification of Highly Potent α-Glucosidase Inhibitors from Artocarpus integer and Molecular Docking Studies

Chem Biodivers. 2021 Dec;18(12):e2100499. doi: 10.1002/cbdv.202100499. Epub 2021 Nov 11.

Abstract

A new natural Diels-Alder adduct (3) was isolated from the leaves and stem bark of Artocarpus integer, along with seventeen known compounds (1, 2, and 4-18). Structural elucidation was conducted using NMR and HR-ESI-MS data, and comparisons were made with previous studies. Deoxyartonin I (3) exhibited the most potent α-glucosidase inhibition (IC50 7.80±0.1 μM), outperforming the acarbose positive control. This was mixed-mode inhibition, as indicated by the intersect in the second quadrant of each respective plot. An in silico molecular docking model and the pharmacokinetic features of 3 suggest that it is a potential inhibitor of enzyme α-glucosidase, and is therefore a lead candidate as a drug against diabetes mellitus.

Keywords: Artocarpus integer; Moraceae; molecular docking model; α-glucosidase inhibition.

MeSH terms

  • Artocarpus / chemistry*
  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / isolation & purification
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • Humans
  • Molecular Docking Simulation*
  • Plant Components, Aerial / chemistry
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • alpha-Glucosidases / metabolism*

Substances

  • Glycoside Hydrolase Inhibitors
  • Plant Extracts
  • alpha-Glucosidases