Zhen Wang,Xiaoqing Li,Menghan Chen,Feiyan Liu,Chao Han,Lingyi Kong,Jianguang Luo
A new method based on ligand fishing combined with high-performance liquid chromatography quadrupole-time-of-flight mass spectrometer and molecular docking was established to screen α -glucosidase inhibitors from a traditional Chinese medicine Morus alba root bark. α -Glucosidase was immobilized on magnetic nanoparticles , used as a solid support to incubate with crude extract. After ligand fishing, the eluates were analyzed by high-performance liquid chromatography quadrupole-time-of-flight mass spectrometer, obtaining eleven ligands ( 1 – 4 , 6 – 12 ) eventually. In order to discriminate the non-specific binders and discover powerful enzyme inhibitors , molecular docking was further performed and three of the eleven ligands were optimized to be excellent α -glucosidase inhibitors by the confirmation of isolation and bioassay of individual compounds. These three ligands, sanggenons G ( 6 ), O ( 7 ) and sanggenol G ( 12 ) exhibited striking inhibitory activities with extremely low IC 50 values. The results suggest that established method will be applied to a wide range of target protein to screen potential bioactive constituents from herbal medicines.
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). Compounds1–16were tested for their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds1and4showed weak BChE-inhibitory activity (IC5045.5 and 61.0 μM); six 2-arylbenzofuran derivatives showed more-potent BChE-inhibitory activity (IC502.5–32.8 μM) than the positive control galantamine (IC5035.3 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.
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