Abstract：OBJECTIVE To design and synthesize flavonoid-polyamine derivatives and investigate their cholinesterase inhibitory activity and cytotoxicity in vitro. METHODS The target compounds were synthesized in five steps from the starting material resorcinol. Their inhibitory activity of acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) were screened by Ellman method. The interaction mode with AChE was studied by enzyme kinetics and molecular docking method. The in vitro toxicity against human hepatocarcinoma (HepG2) and rat pheochromocytoma (PC12) was evaluated by MTT assay. RESULTS Seven novel compounds were obtained, and their structures were confirmed by 1H-NMR, ESI-MS and elemental analysis. In vitro bioassay indicated that these compounds had stronger AChE inhibitory activity than the commercial drug rivastigmine, and compound 6g showed strongest activity on AChE with the IC50 value 0.65 μmol·L-1. Enzyme kinetics and molecular modeling RESULTS showed that the interaction type of compound 6g with AChE was mixed-type inhibition. Besides, these compounds did not show obvious toxicity against HepG2 and PC12 cell lines at the concentration of 100 μmol·L-1. CONCLUSION These series of compounds show preferable inhibition for cholinesterases, which are worthy of further study.
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