Synthesis, biological evaluation of 9-N-substituted berberine derivatives as multi-functional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation

Eur J Med Chem. 2011 Dec;46(12):5885-93. doi: 10.1016/j.ejmech.2011.09.051. Epub 2011 Oct 5.

Abstract

A series of 9-N-substituted berberine derivatives were synthesized and biologically evaluated as antioxidant and inhibitors of acetylcholinesterase (AChE), butyrylcholinesterase and amyloid-β aggregation. Most of these compounds exhibited very good antioxidant activities, inhibitive activities of AChE and amyloid-β aggregation. Among them, compound 8d, (o-methylphenethyl)amino linked at the 9-position of berberine, was found to be a good antioxidant (with 4.05 μM of Trolox equivalents), potent inhibitor of AChE (an IC(50) value of 0.027 μM), and high active inhibitor of amyloid-β aggregation (an IC(50) value of 2.73 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry*
  • Antioxidants / pharmacology*
  • Berberine / analogs & derivatives*
  • Berberine / chemical synthesis
  • Berberine / pharmacology*
  • Butyrylcholinesterase / metabolism
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology*
  • Electrophorus
  • Horses
  • Humans
  • Models, Molecular

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Cholinesterase Inhibitors
  • Berberine
  • Acetylcholinesterase
  • Butyrylcholinesterase