Design, synthesis and evaluation of difunctionalized 4-hydroxybenzaldehyde derivatives as novel cholinesterase inhibitors.

Liang Yu, Rihui Cao, Wei Yi, Qin Yan, Zhiyong Chen, Lin Ma, Huacan Song

School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.

Chemical & pharmaceutical bulletin 2010 Sep

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A series of difunctionalized 4-hydroxybenzaldehyde derivatives were designed, synthesized and evaluated as cholinesterase (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)) inhibitors. The results demonstrated that all the compounds had more potent AChE and BChE inhibitory activities than galanthamine-HBr, one of the best cholinesterase inhibitors known so far. The inhibition mechanism revealed that the best active compound 4e displayed a mix-type mode of AChE and BChE by its dual-site interactions with the catalytic triad active center and the peripheral anionic site (PAS) of enzyme. All these data suggested that further development of such compounds may be of interest.

Citation

Liang Yu, Rihui Cao, Wei Yi, Qin Yan, Zhiyong Chen, Lin Ma, Huacan Song. Design, synthesis and evaluation of difunctionalized 4-hydroxybenzaldehyde derivatives as novel cholinesterase inhibitors. Chemical & pharmaceutical bulletin. 2010 Sep;58(9):1216-20