Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)

J Enzyme Inhib Med Chem. 2011 Oct;26(5):643-8. doi: 10.3109/14756366.2010.543420. Epub 2011 Jan 11.

Abstract

According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A- and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC(50) = 0.27 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Chalcones / chemical synthesis*
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Drug Design*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycyrrhiza uralensis / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Chalcones
  • Enzyme Inhibitors
  • 4-hydroxychalcone
  • Amyloid Precursor Protein Secretases