Acetylcholinesterase-inhibitory activity of Iranian plants: Combined HPLC/bioassay-guided fractionation, molecular networking and docking strategies for the dereplication of active compounds

In order to search for discovery of acetylcholinesterase (AChE) inhibitors, as a therapeutic strategy for treatment of the Alzheimer's disease, twenty-five Iranian plants have been evaluated by an in vitro enzymatic Ellman method and molecular docking study. Each plant was successively extracted by n-hexane, ethyl acetate and methanol to obtain a total of 75 extracts. The inhibiting effect of extracts was measured by a colorimetric assay in 96-well microplates. The n-hexane extract of Prangos ferulacea showed the highest AChE inhibitory activity with 75.6% inhibition at a concentration of 50 mu g/mL. The chemical composition of this extract was investigated in detail based on a combination of HPLC/bioassay-guided fractionation and molecular networking techniques. The results led to the identification of seventeen compounds, one of them was a fatty acid derivative, two compounds had flavonoid structure and others were furanocoumarin type compounds. In vitro analysis showed that the subfraction F-10f was the most potent inhibitor against the activity of AChE with an IC50 value of 25.2 mu g/mL and good docking scores of its constituents confirming its high activity. (C) 2018 Elsevier B.V. All rights reserved.