-Methyl Costaricine and Costaricine, Two Potent Butyrylcholinesterase Inhibitors from Gamb.

Studies have been conducted over the last decade to identify secondary metabolites from plants, in particular those from the class of alkaloids, for the development of new anti-Alzheimer's disease (AD) drugs. The genus , comprising a wide range of alkaloids, is a promising source for the discovery of new cholinesterase inhibitors, the first-line treatment for AD. With regard to this, a phytochemical investigation of the dichloromethane extract of the bark of Gamb. was conducted. Repeated column chromatography and preparative thin-layer chromatography led to the isolation of a new bisbenzylisoquinoline alkaloid, -methyl costaricine (), together with costaricine (), hernagine (), -methyl hernagine (), corydine (), and oxohernagine (). Their structures were elucidated by the 1D- and 2D-NMR techniques and LCMS-IT-TOF analysis. Compounds and were more-potent BChE inhibitors than galantamine with IC values of 3.51 ± 0.80 µM and 2.90 ± 0.56 µM, respectively. The Lineweaver-Burk plots of compounds and indicated they were mixed-mode inhibitors. Compounds and have the potential to be employed as lead compounds for the development of new drugs or medicinal supplements to treat AD.