Synthesis and acetylcholinesterase inhibitory activity of polymethoxyflavone Mannich base derivatives

Abstract

A series of novel polymethoxyflavone Mannich base derivatives 1―8 was synthesized by Mannich reaction of 5-hydroxy-3,7,3′,4′-tetramethoxyflavone 9 with various secondary aliphatic amines and formaldehyde. Their acetylcholinesterase(AChE) inhibitory activities were evaluated. The results showed that most of them exhibited AChE inhibitory activity and especially piperidin-1-yl methyl substituent derivative 5(IC₅₀=0.238 μmol/L) demonstrated stronger activity comparable with the positive control, neoeserinemethyl sulfate(IC₅₀=1.39 μmol/L), which is worthy of further development as an agent for Alzheimer’s disease treatment.

Keywords

Polymethoxyflavone / Mannich base derivative / Acetylcholinesterase inhibitory activity

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