Bis-huperzine B: highly potent and selective acetylcholinesterase inhibitors.
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.
Feng
Song
S
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.
Wang
Zhifei
Z
He
Xuchang
X
Zheng
Suxin
S
Xia
Yu
Y
Jiang
Hualiang
H
Tang
Xican
X
Bai
Donglu
D
D000110:Acetylcholinesterase / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry; D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D029542:Lycopodiaceae; D008958:Models, Molecular; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000470:Alkaloids; D001952:Bridged-Ring Compounds; D002800:Cholinesterase Inhibitors; D011728:Pyridones; C497146:bis(18)-huperzine B; C053016:huperzine B; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase