Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase

Med Chem. 2005 May;1(3):287-91. doi: 10.2174/1573406053765503.


The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. John's wort), was recently identified as potent and direct inhibitor of 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes. In this study, naturally occurring analogues of hyperforin, isolated from H. perforatum, as well as a series of synthetic derivatives obtained by chemical modification of hyperforin by acylation, alkylation or oxidation, were analysed for the inhibition of 5-LO. The efficacies of these compounds were evaluated in intact human polymorphonuclear leukocytes, but also the inhibitory effects on isolated recombinant human 5-LO were investigated. Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects.

Publication types

  • Comparative Study

MeSH terms

  • Bridged Bicyclo Compounds / chemistry
  • Cells, Cultured
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Hypericum / chemistry*
  • Lipoxygenase Inhibitors*
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / chemistry
  • Terpenes / chemistry*


  • Bridged Bicyclo Compounds
  • Enzyme Inhibitors
  • Lipoxygenase Inhibitors
  • Terpenes
  • Phloroglucinol
  • hyperforin