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Development of a multivalent acetylcholinesterase inhibitor via dynamic combinatorial chemistry
Jintao Xu1, Shuang Zhao1, Shixin Zhang1
1School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
Abstract:
In this study, we report the generation of a polymer based dynamic combinatorial library (DCL) using aldehyde-functionalized linear poly(glycidol) and hydrazide derivatives as initial building blocks. In combination with tetrameric acetylcholinesterase (AChE), a certain type of amplified acylhydrazone side chain is identified and further used for the synthesis of a multivalent AChE inhibitor. The cytotoxicity and inhibition properties of the multivalent inhibitor are evaluated, and the results indicate superior bioactivity compared to the commercial reference Edrophonium chloride.
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