Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors

Song Feng; Zhifei Wang; Xuchang He; Suxin Zheng; Yu Xia; Hualiang Jiang; Xican Tang; Donglu Bai

doi:10.1021/jm0496178

Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors

J Med Chem. 2005 Feb 10;48(3):655-7. doi: 10.1021/jm0496178.

Authors

Song Feng¹, Zhifei Wang, Xuchang He, Suxin Zheng, Yu Xia, Hualiang Jiang, Xican Tang, Donglu Bai

Affiliation

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang, 201203, Shanghai.

PMID: 15689148
DOI: 10.1021/jm0496178

Abstract

By targeting dual active sites of AChE, a series of bis-huperzine B analogues with various lengths of the tether were designed, synthesized, and tested for their inhibition and selectivity. The most potent bis-huperzine B (5g) exhibited 3900-fold increase in AChE inhibition and 930-fold greater in selectivity for AChE vs BuChE than its parent huperzine B.

MeSH terms

Acetylcholinesterase / chemistry
Alkaloids / chemistry
Animals
Bridged-Ring Compounds / chemical synthesis*
Bridged-Ring Compounds / chemistry
Bridged-Ring Compounds / pharmacology
Butyrylcholinesterase / chemistry
Catalytic Domain
Cholinesterase Inhibitors / chemical synthesis*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / pharmacology
In Vitro Techniques
Lycopodiaceae
Models, Molecular
Pyridones / chemical synthesis*
Pyridones / chemistry
Pyridones / pharmacology
Rats
Structure-Activity Relationship

Substances

Alkaloids
Bridged-Ring Compounds
Cholinesterase Inhibitors
Pyridones
bis(18)-huperzine B
huperzine B
Acetylcholinesterase
Butyrylcholinesterase