Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry
Shuang Zhao1, Jintao Xu1, Shixin Zhang1
1School of Pharmacy, Jiangsu University, 301 Xuefu Rd., Zhenjiang, China.
Abstract:
In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).
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