Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders

J Med Chem. 2015 Aug 27;58(16):6710-5. doi: 10.1021/acs.jmedchem.5b00958. Epub 2015 Aug 17.

Abstract

Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent γ-carbolinium salts as potent inihitors of both cholinesterases, N-methyl-D-aspartate receptors, and monoamine oxidases. Homobivalent γ-carbolines displayed similar structure-activity relationships on all tested targets and may present promising designed multiple ligands for the treatment of neurodegenerative disorders.

MeSH terms

  • Animals
  • Carbolines / chemical synthesis*
  • Carbolines / therapeutic use*
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / pharmacology
  • Computational Biology
  • Excitatory Amino Acid Antagonists / chemical synthesis
  • Excitatory Amino Acid Antagonists / pharmacology
  • Humans
  • Indicators and Reagents
  • Ligands
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / pharmacology
  • Neurodegenerative Diseases / drug therapy*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Carbolines
  • Cholinesterase Inhibitors
  • Excitatory Amino Acid Antagonists
  • Indicators and Reagents
  • Ligands
  • Monoamine Oxidase Inhibitors
  • Receptors, N-Methyl-D-Aspartate