Cui_2024_Molecules_29_

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 microM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC(50) 2.5-32.8 microM) than the positive control galantamine (IC(50) 35.3 microM), 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 microM. 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.