3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(2-hydroxy)ethyl

• 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: 3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(2-hydroxy)ethyl
• 英文别名: (2R,4aS,6aR,6aS,14aS,14bR)-10-hydroxy-N-(2-hydroxyethyl)-2,4a,6a,6a,9,14a-hexamethyl-11-oxo-1,3,4,5,6,13,14,14b-octahydropicene-2-carboxamide
• 化学式: C₃₁H₄₃NO₄
• 分子量: 493.687
• InChiKey: BJYZENDLYHSAQT-ZRCCSVPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  86.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  雷公藤红素 、 C.I.酸性橙108 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以38%的产率得到3-hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(2-hydroxy)ethyl
  参考文献：
  名称：

  Design and synthesis of celastrol derivatives as anticancer agents

  摘要：

  A series of celastrol derivatives as potential telomerase inhibitors were designed and synthesized. The bioassays demonstrated that title compounds displayed potent anticancer activities against SGC-7901, SMMC-7721, MGC-803 and HepG-2 cell lines, among them, compounds 3c and 3d which containing hydrophilicity moieties exhibited high anti-proliferative activities (IC50 = 0.10-1.22 mu M). The preliminary mechanism of antitumor action indicated that title compound 3c could induce significant SMMC-7721 cells apoptosis. A modified TRAP assay showed that compounds 3c and 3d displayed the most potent inhibitory activity with IC50 values at 0.11 and 0.34 mu M, respectively. And there was a good correlation between telomerase inhibition and anti-proliferative inhibition of SMMC-7721 cells. Moreover, molecular docking indicated that the active compound 3c was nicely bound into the telomerase hTERT active site, hydrophobic, van der Waals and two hydrogen bond interactions with conserved residues ASP 628 and TYR 949 were found. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.039

文献信息

• Reagents, compositions and methods for improving viability and function of cells, tissues and organs
  申请人：Der Sarkissian Shant

  公开号：US11446265B2

  公开（公告）日：2022-09-20

  Compounds, compositions and methods for improving the viability and/or function of cells or for the in vitro, ex vivo or in vivo protection of cells, tissue, graft or organs from various damages are described. The reagents and composition are based on activation of the heat shock response and/or the antioxidant response and include for example, HSP90 co-factor inhibitor such as Celastrol or Celastrol analogs used alone or in combination with an adjunct agent (e.g., a NRF-2 activator, antioxidant, etc.). Therapeutic enhancement may also include increase in paracrine effector production and signaling. Methods for improving the resistance of cells, tissue, grafts or organs to damages or stress, such as hypoxic or oxidative stress-induced cell death, and/or for improving the viability and retention of transplanted or transfused cells are also described. Therapeutic treatment or prevention of ischemic injury (e.g. myocardial infarct, ischemia/reperfusion injury) and related stressors (hypoxia, oxidative stress, inflammation, sepsis/shock, etc) are also provided.

  本文描述了用于提高细胞活力和/或功能，或用于体外、体内或体内保护细胞、组织、移植物或器官免受各种损伤的化合物、组合物和方法。这些试剂和组合物以激活热休克反应和/或抗氧化反应为基础，例如包括单独使用或与辅助剂（如 NRF-2 激活剂、抗氧化剂等）结合使用的 HSP90 协同因子抑制剂，如 Celastrol 或 Celastrol 类似物。治疗增强还可包括增加旁分泌效应物质的产生和信号传递。还描述了提高细胞、组织、移植物或器官对损伤或应激（如缺氧或氧化应激诱导的细胞死亡）的抵抗力，和/或提高移植或输注细胞的存活率和保留率的方法。还提供了对缺血性损伤（如心肌梗塞、缺血/再灌注损伤）和相关应激源（缺氧、氧化应激、炎症、败血症/休克等）的治疗或预防。
• REAGENTS, COMPOSITIONS AND METHODS FOR IMPROVING VIABILITY AND FUNCTION OF CELLS, TISSUES AND ORGANS
  申请人：Der Sarkissian Shant

  公开号：US20210169830A1

  公开（公告）日：2021-06-10

  Compounds, compositions and methods for improving the viability and/or function of cells or for the in vitro, ex vivo or in vivo protection of cells, tissue, graft or organs from various damages are described. The reagents and composition are based on activation of the heat shock response and/or the antioxidant response and include for example, HSP90 co-factor inhibitor such as Celastrol or Celastrol analogs used alone or in combination with an adjunct agent (e.g., a NRF-2 activator, antioxidant, etc.). Therapeutic enhancement may also include increase in paracrine effector production and signaling. Methods for improving the resistance of cells, tissue, grafts or organs to damages or stress, such as hypoxic or oxidative stress-induced cell death, and/or for improving the viability and retention of transplanted or transfused cells are also described. Therapeutic treatment or prevention of ischemic injury (e.g. myocardial infarct, ischemia/reperfusion injury) and related stressors (hypoxia, oxidative stress, inflammation, sepsis/ shock, etc) are also provided.
• [EN] REAGENTS, COMPOSITIONS AND METHODS FOR IMPROVING VIABILITY AND FUNCTION OF CELLS, TISSUES AND ORGANS<br/>[FR] RÉACTIFS, COMPOSITIONS ET PROCÉDÉS POUR AMÉLIORER LA VIABILITÉ ET LA FONCTIONNALITÉ DE CELLULES, TISSUS ET ORGANES
  申请人：DER SARKISSIAN SHANT

  公开号：WO2017214709A1

  公开（公告）日：2017-12-21

  Compounds, compositions and methods for improving the viability and/or function of cells or for the in vitro, ex vivo or in vivo protection of cells, tissue, graft or organs from various damages are described. The reagents and composition are based on activation of the heat shock response and/or the antioxidant response and include for example, HSP90 co-factor inhibitor such as Celastrol or Celastrol analogs used alone or in combination with an adjunct agent (e.g., a NRF-2 activator, antioxidant, etc.). Therapeutic enhancement may also include increase in paracrine effector production and signaling. Methods for improving the resistance of cells, tissue, grafts or organs to damages or stress, such as hypoxic or oxidative stress-induced cell death, and/or for improving the viability and retention of transplanted or transfused cells are also described. Therapeutic treatment or prevention of ischemic injury (e.g. myocardial infarct, ischemia/reperfusion injury) and related stressors (hypoxia, oxidative stress, inflammation, sepsis/ shock, etc) are also provided.
• Design and synthesis of celastrol derivatives as anticancer agents
  作者：Wen-Jian Tang、Jing Wang、Xu Tong、Jing-Bo Shi、Xin-Hua Liu、Jun Li

  DOI：10.1016/j.ejmech.2015.03.039

  日期：2015.5

  A series of celastrol derivatives as potential telomerase inhibitors were designed and synthesized. The bioassays demonstrated that title compounds displayed potent anticancer activities against SGC-7901, SMMC-7721, MGC-803 and HepG-2 cell lines, among them, compounds 3c and 3d which containing hydrophilicity moieties exhibited high anti-proliferative activities (IC50 = 0.10-1.22 mu M). The preliminary mechanism of antitumor action indicated that title compound 3c could induce significant SMMC-7721 cells apoptosis. A modified TRAP assay showed that compounds 3c and 3d displayed the most potent inhibitory activity with IC50 values at 0.11 and 0.34 mu M, respectively. And there was a good correlation between telomerase inhibition and anti-proliferative inhibition of SMMC-7721 cells. Moreover, molecular docking indicated that the active compound 3c was nicely bound into the telomerase hTERT active site, hydrophobic, van der Waals and two hydrogen bond interactions with conserved residues ASP 628 and TYR 949 were found. (C) 2015 Elsevier Masson SAS. All rights reserved.