Rational design and synthesis of highly potent anti-acetylcholinesterase activity huperzine A derivatives.

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Yan J, Sun L, Wu G, Yi P, Yang F, Zhou L, Zhang X, Li Z, Yang X, Luo H, Qiu M

Rational design and synthesis of highly potent anti-acetylcholinesterase activity huperzine A derivatives.

Bioorg Med Chem. 2009 Oct 1;17(19):6937-41. doi: 10.1016/j.bmc.2009.08.017. Epub 2009 Aug 14.

PubMed ID

19726199 [ View in PubMed

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Abstract

By targeting multi-active sites of acetylcholinesterase (AChE), a series of huperzine A (Hup A) derivatives with various aromatic ring groups were designed and synthesized by Schiff reaction. They were evaluated as AChE and butyrylcholinesterase (BChE) inhibitors. Results showed very significant specificity that the group of imine derivatives could inhibit TcAChE and hAChE, but no inhibitory effect on hBChE was detected. The experiment was explained by a docking study. In the docking model, we confirmed that aromatic ring of Hup A derivatives played the pi-pi stacking against aminophenol residues of AChE, and the structure-activity relationship (SAR) was discussed.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Huperzine A	Acetylcholinesterase	IC 50 (nM)	21	N/A	N/A	Details
Tacrine	Acetylcholinesterase	IC 50 (nM)	128	N/A	N/A	Details