Preparation, anticholinesterase activity and molecular docking of new lupane derivatives

Bioorg Med Chem. 2014 Jul 1;22(13):3341-50. doi: 10.1016/j.bmc.2014.04.050. Epub 2014 May 5.

Abstract

A set of twenty one lupane derivatives (2-22) was prepared from the natural triterpenoid calenduladiol (1) by transformations on the hydroxyl groups at C-3 and C-16, and also on the isopropenyl moiety. The derivatives were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and some structure-activity relationships were outlined with the aid of enzyme kinetic studies and docking modelization. The most active compound resulted to be 3,16,30-trioxolup-20(29)-ene (22), with an IC50 value of 21.5μM for butyrylcholinesterase, which revealed a selective inhibitor profile towards this enzyme.

Keywords: Alzheimer’s disease; Cholinesterase inhibitors; Lupane derivatives; Molecular modeling; Triterpenoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Butyrylcholinesterase / blood
  • Butyrylcholinesterase / metabolism*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Eels
  • Horses
  • Kinetics
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Cholinesterase Inhibitors
  • Triterpenes
  • lupane
  • Acetylcholinesterase
  • Butyrylcholinesterase