Design, synthesis and evaluation of novel 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids as potential multifunctional agents for the treatment of Alzheimer's disease

Bioorganic & Medicinal Chemistry Letters
Shixian LiaoZhennan Deng

Abstract

A series of 5,6,7-trimethoxyflavone-6-chlorotacrine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that the target compounds exhibited good acetylcholinesterase (AChE) inhibitory potencies, high selectivity toward AChE over butyrylcholinesterase (BuChE), potential antioxidant activities and significant inhibitory potencies of self-induced beta-amyloid peptide (Aβ) aggregation. In particular, compound 14c had the strongest AChE inhibitory activity with IC50 value of 12.8 nM, potent inhibition of self-induced Aβ1-42 aggregation with inhibition ratio of 33.8% at 25 μM. Moreover, compound 14c acted as an antioxidant, as well as a neuroprotectant. Furthermore, 14c could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 14c might be a potential multifunctional candidate for the treatment of AD.

References

Feb 22, 2008·CNS & Neurological Disorders Drug Targets·Paula I MoreiraGeorge Perry

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Citations

Jan 31, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Wen-Yu WuJin-Ao Duan
Jun 18, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katarina SpilovskaKamil Kuca
Apr 14, 2018·Current Neuropharmacology·Maja PrzybyłowskaIwona Inkielewicz-Stepniak
Sep 20, 2017·Future Medicinal Chemistry·Dawid PanekBarbara Malawska
Jul 29, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Agnieszka Zagórska, Anna Jaromin

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