Hyperforin.
Hyperforin is a polyprenylated acylphloroglucinol derivative from Hypericum perforatum (St. John's wort). It exhibits antidepressant activity by a novel mechanism of action, antibiotic activity against gram-positive bacteria, and antitumoral activity in vivo. However, it also produces drug-drug interactions by activation of the pregnan X receptor. No total synthesis has been described. Some natural and semisynthetic analogues are available to study structure-activity relationships. Enzymatically, the skeleton of hyperforin is formed by isobutyrophenone synthase from isobutyryl-CoA and three molecules of malonyl-CoA. The first prenylation step is catalyzed by a soluble and ion-dependent dimethylallyltransferase. Hyperforin mainly accumulates in pistils and fruits where it probably serves as defensive compound.
Beerhues
Ludger
L
Institut für Pharmazeutische Biologie, Technische Universität Braunschweig, Mendelssohnstr. 1, D-38106 Braunschweig, Germany. l.beerhues@tu-bs.de
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D020902:Hypericum / Q000033:anatomy & histology / Q000737:chemistry* / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013729:Terpenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D001643:Bridged Bicyclo Compounds; D014179:Neurotransmitter Uptake Inhibitors; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin