title: Evaluation of hyperforin analogues for inhibition of 5-lipoxygenase.
abstract: 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.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Feisst
authors.forename: Dana
authors.initials: D
authors.lastname: Albert
authors.forename: Luisella
authors.initials: L
authors.lastname: Verotta
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D016859:Lipoxygenase Inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry; D013729:Terpenes / Q000737:chemistry*
chemical_list: D001643:Bridged Bicyclo Compounds; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin