| Abstract
| - A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory agent in aMagnolia x soulangiana extract using a microplate enzyme assay with Ellman's reagent. This permitted the isolationof the alkaloids taspine (1) and (−)-asimilobine (2), which were detected for the first time in this species. Compound1 showed a significantly higher effect on AChE than the positive control galanthamine and selectively inhibited theenzyme in a long-lasting and concentration-dependent fashion with an IC50 value of 0.33 ± 0.07 μM. Extensive moleculardocking studies were performed with human and Torpedo californica-AChE employing Gold software to rationalizethe binding interaction. The results suggested ligand 1 to bind in an alternative binding orientation when compared togalanthamine. While this is located in close vicinity to the catalytic amino acid triad, the 1−AChE complex was foundto be stabilized by (i) sandwich-like π-stacking interactions between the planar aromatic ligand (1) and the Trp84 andPhe330 of the enzyme, (ii) an esteratic site anchoring with the amino side chain, and (iii) a hydrogen-bonding network.
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