title: Gypsogenin derivatives: an unexpected class of inhibitors of cholinesterases.
abstract: Gypsogenin (1) was obtained by acidic hydrolysis from its saponin. While the parent compound 1 acted as a selective inhibitor for butyrylcholinesterase (from equus) possessing a moderate mixed-type inhibition of the enzyme, Ki values as low as 2.67 ± 0.59 μM were determined for (3β,4α) 3-O-acetyl-olean-12-ene-23,28-dinitrile (11) and acetylcholinesterase (AChE, from electric eel). Thus, 11 possesses one-fifth of the inhibitory activity of the "gold standard" galantamine hydrobromide; this compound is one of the first pentacyclic triterpenoids described as a potent AChE-selective inhibitor.
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heller
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.forename: Björn A
authors.initials: BA
authors.lastname: Weber
authors.forename: René
authors.initials: R
authors.lastname: Csuk
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004593:Electrophorus; D029941:Fish Proteins / Q000378:metabolism; D005702:Galantamine / Q000494:pharmacology; D019073:HT29 Cells; D006367:HeLa Cells; D006736:Horses; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D015394:Molecular Structure; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D029941:Fish Proteins; D012503:Saponins; D005702:Galantamine; C000595883:gypsogenin; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase
keywords: Acetylcholinesterase; Alzheimer's disease; Anticancer activity