Title: Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin Liu HR, Men X, Gao XH, Liu LB, Fan HQ, Xia XH, Wang QA Ref: Nat Prod Res, :1, 2017 : PubMed
Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC50 for AChE = 0.82 +/- 0.08 mumol*L-1, IC50 for BuChE = 46.30 +/- 3.26 mumol*L-1) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC50 for AChE = 10.54 +/- 0.86 mumol*L-1, IC50 for BuChE = 0.26 +/- 0.08 mumol*L-1). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.
        
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Liu HR, Men X, Gao XH, Liu LB, Fan HQ, Xia XH, Wang QA (2017) Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin Nat Prod Res -5
Liu HR, Men X, Gao XH, Liu LB, Fan HQ, Xia XH, Wang QA (2017) Nat Prod Res -5