dispirocyclopropyldehydrocostus lactone | 1403389-47-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: dispirocyclopropyldehydrocostus lactone
• CAS: 1403389-47-8
• 化学式: C₁₇H₂₂O₂
• 分子量: 258.36
• InChiKey: GQIAACVWMZBULU-CRWXNKLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  dispirocyclopropyldehydrocostus lactone 在 叠氮基三甲基硅烷 、 溶剂黄146 、 三乙胺 作用下， 生成
  参考文献：
  名称：

  倍半萜内酯类化合物及其衍生物在制备药物中 的用途

  摘要：

  本发明涉及倍半萜内酯类化合物及其衍生物在制备药物中的用途，属于药物技术领域，具体涉及式(I)化合物在制备药物中的用途，特别是在制备治疗类风湿性关节炎、通过抑制癌症干细胞用于治疗癌症的药物中的用途。

  公开号：

  CN103417532B
• 作为产物：
  描述：

  去氢木香内酯 在 diethylzinc 、 sodium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 dispirocyclopropyldehydrocostus lactone
  参考文献：
  名称：

  Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells

  摘要：

  糖尿病肾病（DN）是糖尿病最常见且严重的慢性并发症之一，但目前尚无有效的临床药物可用于DN的治疗。我们选择并合成了几种倍半萜内酯（SLs），然后使用MTT法检测大鼠系膜细胞（MCs）的增殖，采用ELISA法测量单核细胞趋化蛋白-1（MCP-1）、转化生长因子β（TGF-β1）和纤维连接蛋白（FN）的表达水平，利用实时荧光定量PCR分析测定MCP-1和TGF-β1基因表达，采用西方印迹法检测IκBα蛋白水平，电泳迁移率实验（EMSA）检测核因子κB（NF-κB）的活化。我们发现，倍半萜内酯（如巴特诺里德（PTL）、米克希而内酯（MCL）、阿尔格拉滨和异阿兰酯（IAL））及其几种合成类似物能够有效减弱高糖刺激下大鼠系膜细胞（MCs）中NF-κB的活化、IκBα的降解，以及MCP-1、TGF-β1和FN的表达。这些发现表明，倍半萜内酯及其衍生物具有作为DN治疗候选药物的潜力。

  DOI：

  10.3390/molecules181013061

文献信息

• USES OF SESQUITERPENE LACTONE COMPOUNDS AND THEIR DERIVATIVES IN DRUGS PREPARATION
  申请人：ACCENDATECH

  公开号：US20160367525A1

  公开（公告）日：2016-12-22

  The present invention relates to the uses of sesquiterpene lactone compounds and their derivatives in preparing drugs. It belongs to the field of drug technology, specifically relates to the uses of the compounds of Formula (I) in preparing the drugs, especially the uses in preparing the drugs to treat rheumatoid arthritis and treat cancers through inhibiting cancer stem cells.

  本发明涉及倍半萜内酯化合物及其衍生物在制备药物中的用途。它属于药物技术领域，具体涉及在制备药物中使用式(I)化合物，特别是在制备用于治疗类风湿关节炎和通过抑制癌干细胞治疗癌症的药物中的用途。
• Uses of sesquiterpene lactone compounds and their derivatives in drugs preparation
  申请人：ACCENDATECH

  公开号：US10463644B2

  公开（公告）日：2019-11-05

  The present invention relates to the uses of sesquiterpene lactone compounds and their derivatives in preparing drugs. It belongs to the field of drug technology, specifically relates to the uses of the compounds of Formula (I) in preparing the drugs, especially the uses in preparing the drugs to treat rheumatoid arthritis and treat cancers through inhibiting cancer stem cells.

  本发明涉及倍半萜内酯化合物及其衍生物在制备药物中的用途。它属于药物技术领域，具体涉及式（I）化合物在制备药物中的用途，尤其是制备治疗类风湿性关节炎和通过抑制癌症干细胞治疗癌症的药物中的用途。
• Dispirocyclopropyldehydrocostus lactone selectively inhibits acute myelogenous leukemia cells
  作者：Ya-Hui Ding、Xue Gao、Jing Long、Bei-Jia Kuang、Yue Chen、Quan Zhang

  DOI：10.1016/j.bmcl.2016.01.046

  日期：2016.2

  Acute myeloid leukemia (AML) is a refractory disease, and the majority of AML patients died from relapse and multidrug resistance. More and more studies demonstrate that AML stem cells play key role in multidrug resistance of AML. Here, we report a derivative of dehydrocostus lactone, that is, dispirocyclopropyldehydrocostus lactone (DDL), showed preferable cytotoxicity against a series of leukemia cell lines and AML stem cells from clinical samples of AML patient. Meanwhile, DDL demonstrated no significant toxicity to normal hematopoietic cells. Therefore, the prodrug of DDL, DMADDL, was evaluated for its in vivo anti-AML activity. The result revealed that DMADDL could inhibit the tumor growth in SCID mice tumorigenicity assay. Further study suggested that DDL induced apoptosis mainly through the up-regulation of apoptosis related protein Bax, followed by the cleavage of caspase-3, caspase-9, and PARP. (C) 2016 Elsevier Ltd. All rights reserved.
• 倍半萜内酯类化合物及其衍生物在制备药物中 的用途
  申请人：天津尚德药缘科技股份有限公司

  公开号：CN103417532B

  公开（公告）日：2016-06-01

  本发明涉及倍半萜内酯类化合物及其衍生物在制备药物中的用途，属于药物技术领域，具体涉及式(I)化合物在制备药物中的用途，特别是在制备治疗类风湿性关节炎、通过抑制癌症干细胞用于治疗癌症的药物中的用途。
• Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells
  作者：Qian-Qian Jia、Jian-Cheng Wang、Jing Long、Yan Zhao、Si-Jia Chen、Jia-Dai Zhai、Lian-Bo Wei、Quan Zhang、Yue Chen、Hai-Bo Long

  DOI：10.3390/molecules181013061

  日期：——

  Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.

  糖尿病肾病（DN）是糖尿病最常见且严重的慢性并发症之一，但目前尚无有效的临床药物可用于DN的治疗。我们选择并合成了几种倍半萜内酯（SLs），然后使用MTT法检测大鼠系膜细胞（MCs）的增殖，采用ELISA法测量单核细胞趋化蛋白-1（MCP-1）、转化生长因子β（TGF-β1）和纤维连接蛋白（FN）的表达水平，利用实时荧光定量PCR分析测定MCP-1和TGF-β1基因表达，采用西方印迹法检测IκBα蛋白水平，电泳迁移率实验（EMSA）检测核因子κB（NF-κB）的活化。我们发现，倍半萜内酯（如巴特诺里德（PTL）、米克希而内酯（MCL）、阿尔格拉滨和异阿兰酯（IAL））及其几种合成类似物能够有效减弱高糖刺激下大鼠系膜细胞（MCs）中NF-κB的活化、IκBα的降解，以及MCP-1、TGF-β1和FN的表达。这些发现表明，倍半萜内酯及其衍生物具有作为DN治疗候选药物的潜力。