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Tacrine–Ferulic Acid–Nitric Oxide (NO) Donor Trihybrids as Potent, Multifunctional Acetyl- and Butyrylcholinesterase Inhibitors

2012; American Chemical Society; Volume: 55; Issue: 9 Linguagem: Inglês

10.1021/jm300106z

1520-4804

Chen Yao, Haopeng Sun, Lei Fang, Mei Liu, Sixun Peng, Hong Liao, Jochen Lehmann, Yihua Zhang,

Alzheimer's disease research and treatments

In search of multifunctional cholinesterase inhibitors as potential anti-Alzheimer drug candidates, tacrine-ferulic acid-NO donor trihybrids were synthesized and tested for their cholinesterase inhibitory activities, release of nitric oxide, vasodilator properties, cognition improving potency, and hepatotoxicity. All of the novel target compounds show higher in vitro cholinesterase inhibitory activity than tacrine. Three selected compounds (3a, 3f, and 3k) produce moderate vasorelaxation in vitro, which correlates with the release of nitric oxide. Compared to its non-nitrate dihybrid analogue (3u), the trihybrid 3f exhibits better performance in improving the scopolamine-induced cognition impairment (mice) and, furthermore, less hepatotoxicity than tacrine.