Synthesis and docking studies of alkylene-linked dimers of (-)-huperzine A.
(-)-Huperzine A (5, HupA), an alkaloid isolated from the herb Huperzia serrata, is a potent, selective and reversible acetylcholinesterase (AchE) inhibitor. Based on the hypothesis with respect to two binding sites in the active gorge of AChE and the good example of bis-tacrine, it was predicted from the docking studies of alkylene-linked dimers of HupA that dimers 6 (n = 5, 7, 9) might have good AChE inhibitory activity. Therefore, six dimers with 7-12 methylene units as tethers were thus prepared. It was found that these dimers were less potent than HupA in inhibition of AChE. The difference of the inhibitory potency between these dimers is coincident with the results of the docking studies.
Jin
Guangyi
G
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Luo
Xiaomin
X
He
Xuchang
X
Jiang
Hualiang
H
Zhang
Haiyan
H
Bai
Donglu
D
D000470:Alkaloids; D000478:Alkylation; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry*; D007202:Indicators and Reagents; D011108:Polymers; D011487:Protein Conformation; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry*; D013619:Tacrine / Q000737:chemistry / Q000494:pharmacology
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D007202:Indicators and Reagents; D011108:Polymers; D012717:Sesquiterpenes; C050426:huperzine A; D013619:Tacrine