Structure-activity relationships of memoquin: Influence of the chain chirality in the multi-target mechanism of action

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4312-5. doi: 10.1016/j.bmcl.2009.05.087. Epub 2009 May 28.

Abstract

The present article expands on the study of structure-activity relationships of the novel class of quinone-bearing polyamines, as multi-target-directed ligands against Alzheimer's disease. Namely, the effect of inserting a methyl substituent at the alpha position of the terminal benzyl amine moieties of lead candidate 1 (memoquin) was evaluated at the multiple targets involved in the multifunctional mechanism of action. The RR stereoisomer 2 resulted more effective than 1 in reverting two important effects mediated by acetylcholinesterase (AChE), that is, acetylcholine hydrolysis and AChE-induced amyloid-beta aggregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Alkanes / chemical synthesis*
  • Alkanes / pharmacology
  • Alzheimer Disease / drug therapy
  • Amines / chemistry
  • Amyloid beta-Peptides / chemistry
  • Animals
  • Dose-Response Relationship, Drug
  • Ethylamines / chemical synthesis*
  • Ethylamines / pharmacology
  • Humans
  • Hydrolysis
  • Inhibitory Concentration 50
  • Mice
  • Models, Chemical
  • Polyamines / chemistry
  • Quinones / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Alkanes
  • Amines
  • Amyloid beta-Peptides
  • Ethylamines
  • Polyamines
  • Quinones
  • memoquin
  • Acetylcholinesterase