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  • [Design, synthesis and evaluation of tacrine-methoxybenzene hybrids as cholinesterases inhibitors].

[Design, synthesis and evaluation of tacrine-methoxybenzene hybrids as cholinesterases inhibitors].

Yao xue xue bao = Acta pharmaceutica Sinica (2012-09-21)
Wen Luo, Yong-Mei Zhao, Zhen Zhang, Ya-Bin Su, Chao-Jie Wang
ABSTRACT

A series of tacrine-methoxybenzene hybrids (5a-5i) were designed, synthesized and evaluated as inhibitors of cholinesterases (ChEs). All the compounds had better ChEs inhibitory activities than tacrine with IC50 values at the nanomolar range. Compound 5h exhibited the strongest inhibition on acetylcholinesterase (AChE) with an IC50 value of 6.74 nmol x L(-1) and compound 5f showed the most potent inhibition on butyrylcholinesterase with IC50 value of 3.83 nmol x L(-1). Kinetic and molecular modeling studies showed that these hybrids targeted both the catalytic active site and the peripheral anionic site of AChE.

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