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Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B.

Abstract：

:Natural (-)-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase (AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were designed and synthesized. The AChE inhibition potency of most derivatives of HupB was enhanced about 2-3 orders of magnitude as compared with the parental HupB. Among bis-HupB derivatives, 12h exhibited the most potent in the AChE inhibition and has been evaluated for its pharmacological actions in vivo on ChE inhibition, cognitive enhancement, and neuroprotection. The docking study on the bis-HupB derivatives 12 series with TcAChE has demonstrated that the ligands bound to the dual-site of the enzyme in different level.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

He XC,Feng S,Wang ZF,Shi Y,Zheng S,Xia Y,Jiang H,Tang XC,Bai D

doi

10.1016/j.bmc.2006.11.009

subject

Has Abstract

pub_date

2007-02-01 00:00:00

pages

1394-408

issue

3

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(06)00934-5

journal_volume

15

pub_type

杂志文章

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