Abstract
The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. Johns 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.
Keywords: hyperforin, hypericum perforatum, 5-lipoxygenase, leukotriene, inflammation, polymorphonuclear leukocyte.
Medicinal Chemistry
Title: Evaluation of Hyperforin Analogues for Inhibition of 5-lipoxygenase
Volume: 1 Issue: 3
Author(s): Christian Feißt, Dana Albert, Luisella Verotta and Oliver Werz
Affiliation:
Keywords: hyperforin, hypericum perforatum, 5-lipoxygenase, leukotriene, inflammation, polymorphonuclear leukocyte.
Abstract: The acylphloroglucinol hyperforin, a constituent of the herb Hypericum perforatum (St. Johns 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.
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Cite this article as:
Feißt Christian, Albert Dana, Verotta Luisella and Werz Oliver, Evaluation of Hyperforin Analogues for Inhibition of 5-lipoxygenase, Medicinal Chemistry 2005; 1 (3) . https://dx.doi.org/10.2174/1573406053765503
DOI https://dx.doi.org/10.2174/1573406053765503 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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