Synthesis and biological evaluation of helicid analogues as novel acetylcholinesterase inhibitors

Eur J Med Chem. 2008 Jan;43(1):166-73. doi: 10.1016/j.ejmech.2007.03.018. Epub 2007 Apr 5.

Abstract

A series of helicid analogues were prepared and evaluated in vitro for the cholinesterase (AChE and BuChE) inhibitory activities via UV spectroscopy. The results indicated that compounds 5, 6d and 8 exhibited potent AChE inhibitory activities with IC(50) values of 0.45+/-0.02microM, 0.49+/-0.02microM, and 0.20+/-0.01microM, respectively. High selectivity for AChE over BuChE was also observed. Kinetic study showed that the mechanism of AChE inhibition of compounds 5, 6d and 8 was all mixed-type.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Benzaldehydes / chemical synthesis*
  • Benzaldehydes / chemistry
  • Benzaldehydes / metabolism
  • Benzaldehydes / pharmacology*
  • Biological Products / chemistry
  • Biological Products / metabolism
  • Biological Products / pharmacology
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology
  • Drug Evaluation, Preclinical
  • Glycosides / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Schiff Bases / chemistry
  • Sensitivity and Specificity
  • Spectrophotometry, Ultraviolet

Substances

  • Benzaldehydes
  • Biological Products
  • Cholinesterase Inhibitors
  • Glycosides
  • Schiff Bases
  • helicide
  • Acetylcholinesterase