Multifunctional mercapto-tacrine derivatives for treatment of age-related neurodegenerative diseases

J Med Chem. 2012 Apr 12;55(7):3588-92. doi: 10.1021/jm300124p. Epub 2012 Mar 28.

Abstract

Cooperating mercapto groups with tacrine in a single molecular, novel multifunctional compounds have been designed and synthesized. These mercapto-tacrine derivatives displayed a synergistic pharmacological profile of long-term potentiation enhancement, cholinesterase inhibition, neuroprotection, and less hepatotoxicity, emerging as promising molecules for the therapy of age-related neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Aging
  • Animals
  • Butyrylcholinesterase / chemistry
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology
  • Cell Line, Tumor
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / pharmacology
  • Humans
  • Liver / drug effects
  • Long-Term Potentiation / drug effects
  • Neurodegenerative Diseases / drug therapy*
  • Neuroprotective Agents / chemical synthesis*
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Sulfhydryl Compounds / chemical synthesis*
  • Sulfhydryl Compounds / pharmacology
  • Tacrine / analogs & derivatives*
  • Tacrine / chemical synthesis*
  • Tacrine / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Sulfhydryl Compounds
  • Tacrine
  • Acetylcholinesterase
  • Butyrylcholinesterase