(+)-Arisugacin A--computational evidence of a dual binding site covalent inhibitor of acetylcholinesterase

Bioorg Med Chem Lett. 2011 May 1;21(9):2687-91. doi: 10.1016/j.bmcl.2010.12.041. Epub 2010 Dec 16.

Abstract

A computation docking study of the highly potent, non-nitrogen containing, acetylcholinesterase inhibitor (+)-arisugacin A is presented. The model suggests that (+)-arisugacin A is a dual binding site covalent inhibitor of AChE. These findings are examined in the context of Alzheimer's disease-modifying therapeutic design. (+)-Arisugacin A's revealed mode of action is unique, and may serve as a basis for the development of AD therapeutics capable of treating the symptomatic aspects of AD, while being neuroprotective with long term efficacy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / drug therapy
  • Binding Sites / drug effects
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / pharmacology
  • Computer Simulation*
  • Inhibitory Concentration 50
  • Models, Biological*
  • Models, Molecular
  • Molecular Structure
  • Pyrans / chemical synthesis*
  • Pyrans / chemistry*
  • Pyrans / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Pyrans
  • arisugacin A