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J Enzyme Inhib Med Chem. 2018 Dec;33(1):290-302. doi: 10.1080/14756366.2017.1412314.

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease.

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a School of Pharmacy , Nanjing University of Chinese Medicine , Nanjing , China.
b Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization , Nanjing University of Chinese Medicine , Nanjing , China.
c State Key Laboratory Cultivation Base for TCM Quality and Efficacy , Nanjing University of Chinese Medicine , Nanjing , China.
d Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing , China.
e Key Laboratory of Biomedical Functional Materials, School of Science , China Pharmaceutical University , Nanjing , China.
f School of Nursing , Nanjing University of Chinese Medicine , Nanjing , China.


Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50 = 10.2 ± 1.2, 16.5 ± 1.7, and 15.3 ± 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.


Cholinesterase inhibitor; cinnamic acid; multi-target ligand; tacrine hybrid

[Indexed for MEDLINE]

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