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, K-i values as low as 2.67 +/- 0.59 mu M were determined for (3 beta, 4 alpha) 3-O-acetylolean- 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.