18β-3-O-(β-carboxypropionyl)-11-oxo-olean-12-en-30-oic acid ethyl ester | 1345513-16-7

• 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: 18β-3-O-(β-carboxypropionyl)-11-oxo-olean-12-en-30-oic acid ethyl ester
• 英文别名: 4-([(3β)-30-ethoxy-11,30-dioxoolean-12-en-3-yl]oxy)-4-oxobutanoic acid；4-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-ethoxycarbonyl-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-4-oxobutanoic acid
• CAS: 1345513-16-7
• 化学式: C₃₆H₅₄O₇
• 分子量: 598.821
• InChiKey: YQEIGSFQEZWSQP-LLVBBBEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  18β-3-O-(β-carboxypropionyl)-11-oxo-olean-12-en-30-oic acid ethyl ester 在 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 17.0h， 生成 18β-3-O-(β-(4'-chlorobenzothiazolyl)amidepropionyl)-11-oxo-olean-12-en-30-oic acid ethyl ester
  参考文献：
  名称：

  Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance

  摘要：

  A series of 18 beta-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.02.021
• 作为产物：
  描述：

  甘草次酸 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 96.0h， 生成 18β-3-O-(β-carboxypropionyl)-11-oxo-olean-12-en-30-oic acid ethyl ester
  参考文献：
  名称：

  Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance

  摘要：

  A series of 18 beta-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.02.021

文献信息

• Synthesis and antitumor activity of ring A modified glycyrrhetinic acid derivatives
  作者：René Csuk、Stefan Schwarz、Bianka Siewert、Ralph Kluge、Dieter Ströhl

  DOI：10.1016/j.ejmech.2011.08.038

  日期：2011.11

  Triterpenoic acids show many pharmacological effects, among them an antiinflammatory or an antitumor activity. One of these, glycyrrhetinic acid (1) is of interest because of its antitumor profile. Glycyrrhetinic acid is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize new derivatives of it-differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/ethidium bromide assay and trypan blue staining. The most active compound, 34, a benzyl glycyrrhetinate holding an extra 3-N-(3-aminopropyl)glycyl substituent showed IC50 between 1.96 and 5.14 mu m for five human cancer cell lines and triggers apoptosis in 80% of the cells. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Discovery of 18β-glycyrrhetinic acid conjugated aminobenzothiazole derivatives as Hsp90-Cdc37 interaction disruptors that inhibit cell migration and reverse drug resistance
  作者：Le Jin、Rizhen Huang、Xiaochao Huang、Bin Zhang、Min Ji、Hengshan Wang

  DOI：10.1016/j.bmc.2018.02.021

  日期：2018.5

  A series of 18 beta-glycyrrhetinic acid (GA) conjugated aminobenzothiazole derivatives were designed, synthesized and evaluated for disruption activity of Hsp90-Cdc37 as well as the effects of in vitro cell migration. These compounds exhibited relatively good disruption activity against Hsp90-Cdc37 with IC50 values in low micromolar range. A docking study of the most active compound 11g revealed key interactions between 11g and Hsp90-Cdc37 complex in which the benzothiazole moiety and the amine chain group were important for improving activity. It is noteworthy that further antitumor activity screening revealed that some compounds exhibited better inhibitory activity than the commercial anticancer drug 5-FU and showed potent suppression activity against drug-resistant cancer cells. In particular, compound 11 g appeared to be the most potent compound against the A549 cell line, at least partly, by inhibition of the activity of Hsp90 and apoptosis induction. The treatment of A549 cells with compound 11g resulted in inhibition of in vitro cell migration through wound healing assay and S phase of cell cycle arrested. In addition, 11g-induced apoptosis was significantly facilitated in A549 cells. Thus, we conclude that GA aminobenzothiazole derivatives may be the potential Hsp90-Cdc37 disruptors with the ability to suppress cells migration and reversed drug-resistant. (C) 2018 Elsevier Ltd. All rights reserved.