Benzofuran Derivatives from Cortex Mori Radicis and Their Cholinesterase-Inhibitory Activity

The phytochemical investigation of Cortex Mori Radicis led to the isolation and identification of a new prenylated benzofuranone ( ) and four ring-opening derivatives ( - ) named albaphenol A-E, as well as nigranol A ( ), together with ten 2-arylbenzofuran derivatives ( - ). The characterization of the structures of the new compounds and the structural revision of nigranol A ( ) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds - were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds and showed weak BChE-inhibitory activity (IC 45.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC 2.5-32.8 μM) than the positive control galantamine (IC 35.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C ( ) exhibited the most potent and selective inhibitory activity against BChE in a competitive manner, with a Ki value of 1.7 μM. The structure-activity relationships of the benzofuran-type stilbenes were discussed. Furthermore, molecular docking and dynamic simulations were performed to clarify the interactions of the inhibitor-enzyme complex.