从细叶乌头中提取的选择性双胆碱酯酶抑制剂。

Selective dual cholinesterase inhibitors from Aconitum laeve.

作者信息

Ahmad Hanif, Ahmad Shujaat, Shah Syed Adnan Ali, Khan Hidayat Ullah, Khan Farman Ali, Ali Mumtaz, Latif Abdul, Shaheen Farzana, Ahmad Manzoor

机构信息

a Department of Chemistry , University of Malakand , Dir (Lower) 18550 , Pakistan.

b Department of Pharmacy , Shaheed Benazir Bhutto University Sheringal , Dir (Upper) 18000 , Pakistan.

出版信息

J Asian Nat Prod Res. 2018 Feb;20(2):172-181. doi: 10.1080/10286020.2017.1319820. Epub 2017 May 2.

DOI:10.1080/10286020.2017.1319820

PMID:28463565

Abstract

New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1-6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1-6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC= 3.7 μM, 4.53 μM) and BChE (IC= 12.23 μM, 9.94 μM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC= 2.51 and 6.13 μM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.

摘要

从光滑乌头的根中分离出新型牛扁碱型双胆碱酯酶抑制剂斯瓦廷宁 - C（1），以及三种已知的降二萜生物碱霍内卡林（2）、阿替新碱（5）和拉帕乌头碱（6），还有两种合成已知但植物化学上为新的苯衍生物，2 - 乙酰氨基苯甲酸甲酯（3）和4 - [2 - （甲氧基羰基）苯胺基] - 4 - 氧代丁酸甲酯（4）。基于最新的光谱技术并与文献中的现有数据进行仔细比较，确定了新化合物和已知化合物（1 - 6）的结构。在体外，测试了化合物（1 - 6）对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BChE）的抑制活性。化合物1和2分别对AChE（IC = 3.7 μM，4.53 μM）和BChE（IC = 12.23 μM，9.94 μM）表现出竞争性抑制。化合物5和6仅对AChE表现出有前景的非竞争性抑制模式（IC = 2.51和6.13 μM）。化合物3和4对AChE和BChE均表现出较弱的抑制作用。