Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety.
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.
Verotta
Luisella
L
Dipartimento di Chimica Organica e Industriale, Università di Milano, Via Venezian 21, 20133 Milano, Italy. luisella.verotta@unimi.it
Appendino
Giovanni
G
Belloro
Emanuela
E
Bianchi
Federica
F
Sterner
Olov
O
Lovati
Marco
M
Bombardelli
Ezio
E
D000818:Animals; D001921:Brain / Q000187:drug effects; D001643:Bridged Bicyclo Compounds; D002855:Chromatography, Thin Layer; D003510:Cyclohexanes / Q000737:chemistry / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020902:Hypericum / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D010696:Phloroglucinol / Q000031:analogs & derivatives; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D001643:Bridged Bicyclo Compounds; D003510:Cyclohexanes; D018492:Dopamine Antagonists; D010696:Phloroglucinol; D017981:Receptors, Neurotransmitter; D017367:Selective Serotonin Reuptake Inhibitors; D013729:Terpenes; C455160:hyperforin 3,5-dinitrobenzoate; C455159:hyperforin acetate; C455161:hyperforin trimethoxybenzoate; C001654:hyperforin