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Bioorg Med Chem Lett. 2016 May 15;26(10):2539-2543. doi: 10.1016/j.bmcl.2016.03.086. Epub 2016 Mar 25.

Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.

Author information

1
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
2
Nanyang City Center Hospital, Nanyang 473061, China.
3
West China Hospital, Sichuan University, Chengdu 610041, China.
4
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China. Electronic address: liuwm1969@163.com.
5
College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China. Electronic address: sangzhipei@163.com.

Abstract

A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7μM) and self-induced β-amyloid (Aβ1-42) aggregation (30.8-39.1%, 25μM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2μM), and Aβ1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aβ aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.

KEYWORDS:

AChE inhibitor; Alzheimer’s disease; Antioxidant; Aβ aggregation inhibitor; Hybrids; Neuroprotectant

PMID:
27072909
DOI:
10.1016/j.bmcl.2016.03.086
[Indexed for MEDLINE]

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