Erinacerins C-L, isoindolin-1-ones with α-glucosidase inhibitory activity from cultures of the medicinal mushroom Hericium erinaceus

J Nat Prod. 2015 Jan 23;78(1):146-54. doi: 10.1021/np5004388. Epub 2015 Jan 7.

Abstract

The well-known edible and medicinal mushroom Hericium erinaceus produces various bioactive secondary metabolites. Ten new isoindolin-1-ones, named erinacerins C-L (1-10), together with (E)-5-(3,7-dimethylocta-2,6-dien-1-yl)-4-hydroxy-6-methoxy-2-phenethylisoindolin-1-one (11) were isolated from the solid culture of H. erinaceus. The structures of new metabolites were established by spectroscopic methods. The absolute configurations of 3, 4, 9, and 10 were assigned by comparing their specific rotations with those of related phthalimidines (13-20). Compounds 5 and 6, 7 and 8, and 9 and 10 are double-bond positional isomers. In a α-glucosidase inhibition assay, compounds 2-11 showed inhibitory activity with IC50 values ranging from 5.3 to 145.1 μM. Preliminary structure-activity analysis indicated that the terpenoid side chain and the phenolic hydroxy groups contributed greatly to the α-glucosidase inhibitory activity of 1-11. In a cytotoxicity assay, compound 11 also presented weak cytotoxicity against two cell lines, A549 and HeLa, with IC50 values of 49.0 and 40.5 μM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology*
  • Drug Screening Assays, Antitumor
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / isolation & purification*
  • Glycoside Hydrolase Inhibitors / pharmacology*
  • HeLa Cells
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Heterocyclic Compounds, 3-Ring / isolation & purification*
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Isoindoles / chemistry
  • Isoindoles / isolation & purification*
  • Isoindoles / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-Glucosidases / drug effects*

Substances

  • (E)-5-(3,7-dimethylocta-2,6-dien-1-yl)-4-hydroxy-6-methoxy-2-phenethylisoindolin-1-one
  • Antineoplastic Agents
  • Glycoside Hydrolase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Isoindoles
  • erinacerin A
  • alpha-Glucosidases