Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety

J Nat Prod. 2002 Apr;65(4):433-8. doi: 10.1021/np0105681.

Abstract

Modification of the St. John's wort acylphloroglucinol constituent, hyperforin (1), by acylation, alkylation, and oxidation resulted in detrimental effects on the inhibition of the synaptosomal accumulation of serotonin, showing the existence of definite structure-activity relationships in this in vitro test system and highlighting the role of the enolized cyclohexanedione moiety for activity on neurotransmitter reuptake.

MeSH terms

  • Animals
  • Brain / drug effects
  • Bridged Bicyclo Compounds
  • Chromatography, Thin Layer
  • Cyclohexanes / chemistry
  • Cyclohexanes / pharmacology
  • Dopamine Antagonists / chemical synthesis
  • Dopamine Antagonists / chemistry
  • Dopamine Antagonists / pharmacology
  • Hypericum / chemistry*
  • Inhibitory Concentration 50
  • Molecular Conformation
  • Phloroglucinol / analogs & derivatives
  • Plants, Medicinal / chemistry*
  • Rats
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis*
  • Selective Serotonin Reuptake Inhibitors / chemistry
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Spectrophotometry, Infrared
  • Structure-Activity Relationship
  • Terpenes / chemical synthesis*
  • Terpenes / chemistry*
  • Terpenes / pharmacology

Substances

  • Bridged Bicyclo Compounds
  • Cyclohexanes
  • Dopamine Antagonists
  • Receptors, Neurotransmitter
  • Serotonin Uptake Inhibitors
  • Terpenes
  • hyperforin 3,5-dinitrobenzoate
  • hyperforin acetate
  • hyperforin trimethoxybenzoate
  • Phloroglucinol
  • hyperforin