kanglexin

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: kanglexin
• 英文别名: 4-O-(4,5-dihydroxy-7-methyl-9,10-dioxoanthracen-2-yl) 1-O-ethyl butanedioate
• 化学式: C₂₁H₁₈O₈
• 分子量: 398.369
• InChiKey: BPCWYLYZWFBKMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  大黄素 、 monoethyl chloro succinate 在 ammonium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 kanglexin
  参考文献：
  名称：

  Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway

  摘要：

  Hyperlipidaemia is one of the major risk factors for atherosclerosis, coronary heart disease, stroke and diabetes. In the present study, we synthesized a new anthraquinone compound, 1,8-dihydroxy-3-succinic acid monoethyl ester-6-methylanthraquinone, and named it Kanglexin (KLX). The aim of this study was to evaluate whether KLX has a lipid-lowering effect and to explore the potential molecular mechanism. In this study, Sprague-Dawley rats were fed a high fat diet (HFD) for 5 weeks to establish a hyperlipidaemia model; then, the rats were orally administered KLX (20, 40, and 80 mg kg^-1·d^-1) or atorvastatin calcium (AT, 10 mg kg^-1·d^-1) once a day for 2 weeks. KLX had prominent effects on reducing blood lipids, hepatic lipid accumulation, body weight and the ratio of liver weight/body weight. Furthermore, KLXdramatically reduced the total cholesterol (TC) and triglyceride (TG) levels and lipid accumulation in a HepG2 cell model of dyslipidaemia induced by 1 mmol/L oleic acid (OA). KLX may decrease lipid levels by phosphorylating adenosine monophosphate-activated protein kinase (AMPK) and the downstream sterol regulatory element binding protein 2 (SREBP-2)/proprotein convertase subtilisin/kexin type 9 (PCSK9)/low-density lipoprotein receptor (LDLR) signalling pathway in the HFD rats and OA-treated HepG2 cells. The effects of KLX on the AMPK/SREBP-2/PCSK9/LDLR signalling pathway were abolished when AMPK was inhibited by compound C (a specific AMPK inhibitor) in HepG2 cells. In summary, KLX has an efficient lipid-lowering effect mediated by activation of the AMPK/SREBP-2/PCSK9/LDLR signalling pathway. Our findings may provide new insight into and evidence for the discovery of a new lipid-lowering drug for the prevention and treatment of hyperlipidaemia, fatty liver, and cardiovascular disease in the clinic.

  DOI：

  10.1016/j.biopha.2020.110802

文献信息

• 大黄素琥珀酰酯类化合物在制备降血脂药物中的用途
  申请人：江苏康缘药业股份有限公司

  公开号：CN108186623B

  公开（公告）日：2022-12-23

  本发明公开了大黄素琥珀酰酯类化合物在制备降血脂药物中的用途，属于医药技术领域，所述的大黄素琥珀酰酯类化合物具有式I所示的结构(R为C1‑5烷基)。通过对实验混合型高脂血症大鼠进行药理实验，证实本发明的大黄素琥珀酰酯类化合物优于大黄素，具有降血脂作用显著、安全性好、用药简单方便、原料价格低廉易得、便于运输与保存的优点。本发明所提出的大黄素琥珀酰酯类化合物在降血脂药物制备领域将具有广阔的应用前景。
• Emodin succinyl ester compound, preparation method therefor and application thereof
  申请人：JIANGSU KANION PHARMACEUTICAL CO., LTD.

  公开号：US11254635B2

  公开（公告）日：2022-02-22

  Disclosed in the present invention are an emodin succinyl ester compound, a preparation method therefor and a use thereof, the emodin succinyl ester compound having the structure as represented by formula I (R being a C1-5 alkyl group). The method provided in the present invention has a simple method course, and may effectively save time in synthesis and reduce costs, being simple to operate, being easy to implement, and being suitable for industrial production. Experiments show that the emodin succinyl ester compound of the present invention may better promote the healing of diabetic wounds than emodin, and may be used for preparing a drug for promoting the healing of diabetic wounds. Moreover, it has been confirmed by means of performing pharmacological experiments on rats suffering from experimentally mixed hyperlipidemia that the emodin succinyl ester compound of the present invention is superior to emodin, and has the advantages of having a remarkable blood fat lowering effect, being safe, being simple and convenient to administer, the raw materials being low cost and readily available, and being easy to transport and store.

  本发明公开了一种大黄素琥珀酸酯化合物及其制备方法和用途，所述大黄素琥珀酸酯化合物的结构如式I所示（R为C1-5烷基）。本发明提供的方法工艺简单，可有效节省合成时间，降低成本，操作简单，易于实施，适合工业化生产。实验表明，本发明的大黄素琥珀酰酯化合物可比大黄素更好地促进糖尿病伤口愈合，可用于制备促进糖尿病伤口愈合的药物。此外，通过对实验性混合型高脂血症大鼠进行药理实验证实，本发明的大黄素琥珀酰酯化合物优于大黄素，具有降血脂效果显著、安全、用药简单方便、原料成本低易得、运输储存方便等优点。
• EMODIN SUCCINYL ESTER COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
  申请人：JIANGSU KANION PHARMACEUTICAL CO., LTD.

  公开号：US20200399199A1

  公开（公告）日：2020-12-24

  Disclosed in the present invention are an emodin succinyl ester compound, a preparation method therefor and a use thereof, the emodin succinyl ester compound having the structure as represented by formula I (R being a C 1-5 alkyl group). The method provided in the present invention has a simple method course, and may effectively save time in synthesis and reduce costs, being simple to operate, being easy to implement, and being suitable for industrial production. Experiments show that the emodin succinyl ester compound of the present invention may better promote the healing of diabetic wounds than emodin, and may be used for preparing a drug for promoting the healing of diabetic wounds. Moreover, it has been confirmed by means of performing pharmacological experiments on rats suffering from experimentally mixed hyperlipidemia that the emodin succinyl ester compound of the present invention is superior to emodin, and has the advantages of having a remarkable blood fat lowering effect, being safe, being simple and convenient to administer, the raw materials being low cost and readily available, and being easy to transport and store.
• Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway
  作者：Xin Li、Xueling Hu、Tengfei Pan、Lei Dong、Lili Ding、Zhenzhong Wang、Rui Song、Xiuzhu Wang、Ning Wang、Yan Zhang、Jinhui Wang、Baofeng Yang

  DOI：10.1016/j.biopha.2020.110802

  日期：2021.1

  Hyperlipidaemia is one of the major risk factors for atherosclerosis, coronary heart disease, stroke and diabetes. In the present study, we synthesized a new anthraquinone compound, 1,8-dihydroxy-3-succinic acid monoethyl ester-6-methylanthraquinone, and named it Kanglexin (KLX). The aim of this study was to evaluate whether KLX has a lipid-lowering effect and to explore the potential molecular mechanism. In this study, Sprague-Dawley rats were fed a high fat diet (HFD) for 5 weeks to establish a hyperlipidaemia model; then, the rats were orally administered KLX (20, 40, and 80 mg kg^-1·d^-1) or atorvastatin calcium (AT, 10 mg kg^-1·d^-1) once a day for 2 weeks. KLX had prominent effects on reducing blood lipids, hepatic lipid accumulation, body weight and the ratio of liver weight/body weight. Furthermore, KLXdramatically reduced the total cholesterol (TC) and triglyceride (TG) levels and lipid accumulation in a HepG2 cell model of dyslipidaemia induced by 1 mmol/L oleic acid (OA). KLX may decrease lipid levels by phosphorylating adenosine monophosphate-activated protein kinase (AMPK) and the downstream sterol regulatory element binding protein 2 (SREBP-2)/proprotein convertase subtilisin/kexin type 9 (PCSK9)/low-density lipoprotein receptor (LDLR) signalling pathway in the HFD rats and OA-treated HepG2 cells. The effects of KLX on the AMPK/SREBP-2/PCSK9/LDLR signalling pathway were abolished when AMPK was inhibited by compound C (a specific AMPK inhibitor) in HepG2 cells. In summary, KLX has an efficient lipid-lowering effect mediated by activation of the AMPK/SREBP-2/PCSK9/LDLR signalling pathway. Our findings may provide new insight into and evidence for the discovery of a new lipid-lowering drug for the prevention and treatment of hyperlipidaemia, fatty liver, and cardiovascular disease in the clinic.