Inhibitory effect of flavonoids on human glutaminyl cyclase

Bioorg Med Chem. 2016 May 15;24(10):2280-6. doi: 10.1016/j.bmc.2016.03.064. Epub 2016 Apr 1.

Abstract

Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer's disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4' (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure-activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC.

Keywords: Alzheimer’s disease; Enzyme inhibitor; Flavonoids; Glutaminyl cyclase; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / enzymology
  • Aminoacyltransferases / antagonists & inhibitors*
  • Aminoacyltransferases / metabolism
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Flavonoids / chemistry*
  • Flavonoids / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Aminoacyltransferases
  • glutaminyl-peptide cyclotransferase