Gypsogenin derivatives: an unexpected class of inhibitors of cholinesterases

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.