Diterpenoids from Euphorbia fischeriana with Kv1.3 Inhibitory Activity

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2023-10-05 DOI:10.1021/acs.jnatprod.3c00580

Qin Cai, Hong-Jing Zha, Shi-Ying Yuan, Xing Sun, Xin Lin, Xin-Yu Zheng, Ying-Xian Qian, Ru-Feng Xia, Yue-Shan Luo, Zhimian Shi, Jun-Cheng Su* and Luo-Sheng Wan*,

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引用次数: 0

Abstract

Euphorbia diterpenoids possess inhibitory effects of Kv1.3 ion channel, but most of this research has focused on diterpenoids with jatrophane-related or ingenane-related skeletons. In the present study, nine undescribed (1–9) and 16 known (10–25) diterpenoids, based on jatrophane, lathyrane, ingenane, abietane, and atisane skeletons, were identified from the methanol extract of the aerial parts of Euphorbia fischeriana. The structures were established by analysis of the spectroscopic data as well as by single-crystal X-ray diffraction analysis. Among the isolated diterpenoids, macrocyclic jatrophanes and lathyranes exerted Kv1.3 blocking activity. Compound 8 exhibited good selectivity on the inhibition of the Kv 1.3 channel rather than hERG channel, with a selectivity index over 7.0. The selective activity of lathyrane diterpenoids indicates that macrocyclic diterpenoids have the potential to be further investigated as therapeutic agents for the treatment of autoimmune diseases.

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费氏大戟中具有Kv1.3抑制活性的二萜类化合物

大戟二萜类化合物具有Kv1.3离子通道的抑制作用，但大多数研究都集中在具有麻疯树烷相关或天然树烷相关骨架的二萜类药物上。在本研究中，从费氏大戟地上部分的甲醇提取物中鉴定出了9种未描述的（1-9）和16种已知的（10-25）二萜，它们基于麻疯树烷、木脂烷、银杏烷、枞树烷和atisane骨架。通过光谱数据的分析以及单晶X射线衍射分析来建立结构。在分离的二萜类化合物中，大环麻疯树烷和板条烷具有Kv1.3阻断活性。化合物8对Kv 1.3通道而不是hERG通道的抑制表现出良好的选择性，选择性指数超过7.0。板条烷二萜类化合物的选择性活性表明，大环二萜类具有作为治疗自身免疫性疾病的治疗剂进行进一步研究的潜力。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.