当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Bioactivity-guided identification of flavonoids with cholinesterase and β-amyloid peptide aggregation inhibitory effects from the seeds of Millettia pachycarpa.

Bioactivity-guided identification of flavonoids with cholinesterase and β-amyloid peptide aggregation inhibitory effects from the seeds of Millettia pachycarpa.

Abstract：

:Millettia pachycarpa Benth, a widely used anthelminthic drug in folk, is rich in flavonoids with various bioactivities. This study aimed to identify active flavonoids with anti-Alzheimer's disease (AD) effect from its seeds by a bioassay-guided isolation. A novel rotenoid with unusual oxidative ring-opening skeleton (10) and nine known flavonoids (1-9) were obtained, and their structures were elucidated by NMR and HR-ESIMS analysis. Among all isolates, 7 and 8 showed selective butyrylcholinesterase (BChE) inhibitory activities (IC50 = 2.34 and 11.49 μM, respectively), while 3 was classified as a dual-action inhibitor against acetylcholinesterase (AChE) and BChE (IC50 AChE = 17.14 μM, IC50 BChE = 5.68 μM). Further kinetic study revealed that 3, 7, and 8 were mixed-type BChE inhibitors, but 3 was a competitive AChE inhibitor. Their strong binding affinities to BChE were confirmed by fluorescence quenching analysis. Additionally, 3 and 8 exhibited potent inhibitory effects against β-amyloid peptide aggregation. These results revealed M. pachycarpa could be a valuable source for anti-AD leads development, and compounds 3, 7 and 8 were worthy of further study as multifunctional or specific agents for AD treatment.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Tu Y,Wu C,Kang Y,Li Q,Zhu C,Li Y

doi

10.1016/j.bmcl.2019.03.024

subject

Has Abstract

pub_date

2019-05-15 00:00:00

pages

1194-1198

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(19)30162-3

journal_volume

29

pub_type

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