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 ( 1 ) and four ring-opening derivatives ( 2 - 5 ) named albaphenol A-E, as well as nigranol A ( 6 ), together with ten 2-arylbenzofuran derivatives ( 7 - 16 ). The characterization of the structures of the new compounds and the structural revision of nigranol A ( 6 ) were conducted using the comprehensive analysis of spectroscopic data (1D/2D NMR, HRESIMS, CD, and XRD). Compounds 1 - 16 were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1 and 4 showed weak BChE-inhibitory activity (IC 50 45.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC 50 2.5-32.8 μM) than the positive control galantamine (IC 50 35.3 μM), while being inactive or weakly inhibitory toward AChE. Cathafuran C ( 14 ) 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.