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海南油杉中的呋喃甲酸J及其对ATP-柠檬酸裂解酶和乙酰辅酶A羧化酶的双重抑制作用

Fortunefuroic Acid J from Keteleeria Hainanensis and its Dual Inhibitory Effects on ATP-Citrate Lyase and Acetyl-CoA Carboxylase.

作者信息

Zhao Ze-Yu, Zang Yi, Li Jia, Choo Yeun-Mun, Xiong Juan, Hu Jin-Feng

机构信息

Department of Natural Medicine, School of Pharmacy, Fudan University, Shanghai, 201203, P. R. China.

Institute of Natural Medicine and Health Products, School of Pharmaceutical Sciences, Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou University, Zhejiang, 318000, PR China.

出版信息

Chem Biodivers. 2024 Dec;21(12):e202401520. doi: 10.1002/cbdv.202401520. Epub 2024 Oct 26.

Abstract

A previously undescribed triterpenoid (fortunefuroic acid J, 1) was isolated from the endangered conifer Keteleeria hainanensis, along with 20 other known terpenoids. Compound 1 is characterized by an unusual 3,4-seco-9βH-lanost-3-oic acid motif, featuring a rare furoic acid moiety in its lateral chain. The structure elucidation of this compound was achieved through a combination of spectroscopic and computational methods. The C-15 epimers of 15-methoxypinusolidic acid (15R-8 and 15S-9) were successfully separated and identified for the first time. Compound 1 demonstrated dual inhibitory effects against ATP-citrate lyase (ACL, IC: 0.92 μM) and acetyl-CoA carboxylase 1 (ACC1, IC: 10.76 μM). Compounds 2 and 11 exclusively inhibited ACL, exhibiting IC values of 2.64 and 6.35 μM, respectively. Compound 1 is classified among the fortunefuroic acid-type compounds, previously isolated from K. fortunei, distinguished by the presence of a rare furoic acid moiety in their lateral chain. The chemotaxonomic significance of the 9βH-lanost-26-oic acids in Keteleeria was briefly discussed. These findings highlight the importance of conserving plant species diversity, thereby enhancing the exploration of structurally diverse compounds and potential avenues for developing new therapeutics targeting ACL/ACC1-associated diseases.

摘要

从濒危针叶树海南油杉中分离出一种此前未被描述的三萜类化合物(海南呋喃酸J,1)以及其他20种已知的萜类化合物。化合物1的特征是具有一个不寻常的3,4-开环-9βH-羊毛甾-3-酸基序,其侧链含有一个罕见的呋喃酸部分。该化合物的结构解析是通过光谱学和计算方法相结合完成的。首次成功分离并鉴定了15-甲氧基松脂酸的C-15差向异构体(15R-8和15S-9)。化合物1对ATP-柠檬酸裂解酶(ACL,IC:0.92 μM)和乙酰辅酶A羧化酶1(ACC1,IC:10.76 μM)具有双重抑制作用。化合物2和11仅抑制ACL,IC值分别为2.64和6.35 μM。化合物1属于呋喃酸型化合物,此前从金钱松中分离得到,其特征是侧链中存在罕见的呋喃酸部分。简要讨论了海南油杉中9βH-羊毛甾-26-酸的化学分类学意义。这些发现凸显了保护植物物种多样性的重要性,从而加强对结构多样的化合物的探索以及开发针对ACL/ACC1相关疾病的新疗法的潜在途径。

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