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Bioorg Med Chem Lett. 2012 Oct 15;22(20):6498-502. doi: 10.1016/j.bmcl.2012.08.036. Epub 2012 Aug 16.

Design, synthesis and pharmacological evaluation of novel tacrine-caffeic acid hybrids as multi-targeted compounds against Alzheimer's disease.

Author information

1
Department of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

Abstract

A novel series of tacrine-caffeic acid hybrids (5a-f) were designed and synthesized by combining caffeic acid (CA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 5e showed the highest selectivity in inhibiting acetylcholinesterase (AChE) over butyrylcholinesterase (BuChE). Enzyme kinetic study had suggested that 5e binds to both catalytic (CAS) and peripheral anionic sites (PAS) of AChE. Moreover, compound 5e also inhibited self- or AChE-induced β-amyloid(1-40) aggregation, as well as had potent neuroprotective effects against H(2)O(2)- and glutamate- induced cell death with low toxicity in HT22 cells.

PMID:
22981331
DOI:
10.1016/j.bmcl.2012.08.036
[Indexed for MEDLINE]

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