(4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyl amine | 86699-79-8

• 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: (4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyl amine
• 英文别名: (4e,8e,12e,16e)-4,8,13,17,21-Penta-methyl-4,8,12,16,20-docosapentaenylamine；(4E,8E,12E,16E)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-amine
• CAS: 86699-79-8
• 化学式: C₂₇H₄₇N
• 分子量: 385.677
• InChiKey: HXKCSQYTFJVBEN-OGDZRKEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  28
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyl amine 在 sodium acetate 、 乙酸酐 作用下， 以 乙醚 为溶剂， 反应 4.0h， 生成 (4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyl maleimide
  参考文献：
  名称：

  Synthesis and biological activity of a squalenoid maleimide and other classes of squalene derivatives as irreversible inhibitors of 2,3-oxidosqualene cyclase

  摘要：

  New classes of squalene derivatives were rationally designed and synthesized as irreversible inhibitors of 2,3-oxido-squalene cyclase (OSC), a key enzyme in sterol biosynthesis. The derivatives synthesized were maleimide 5, disulfides 8-9, alpha,beta-unsaturated nitriles 10-11 and oxirane 12. The inhibitor activities of these derivatives were determined in vitro on OSC associated with pig liver microsomes. Squalene and dodecyl maleimide were the best inhibitors of OSC, showing a time-dependent enzyme from squalene maleimide inactivation whereas the dodecyl derivative did not. This fact and the complex kinetics shown by squalene maleimide suggest the presence of different classes of thiolic groups essential to the activity of OSC.

  DOI：

  10.1016/0223-5234(94)90121-x
• 作为产物：
  描述：

  1,1',2-trisnorsqualene alcohol 生成 (4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenyl amine
  参考文献：
  名称：

  Trisnorsqualene alcohol, a potent inhibitor of vertebrate squalene epoxidase

  摘要：

  DOI：

  10.1021/ja00186a062

文献信息

• Enhancement of ricin toxin a chain immunotoxin activity: Synthesis, ionophoretic ability, and in vitro activity of monensin derivatives
  作者：Franco Dosio、Antonia Franceschi、Maurizio Ceruti、Paola Brusa、Luigi Cattel、Marco Colombatti

  DOI：10.1016/0006-2952(96)00176-1

  日期：1996.7

  Site-selective toxin delivery was achieved by coupling monoclonal antibody to the A chain subunit of ricin (RTA-IT). The cell-killing potency of RTA-IT can be drastically increased in vitro by using ionophores such as monensin. To reduce the intrinsic toxicity of monensin and to enhance its in vitro and in vivo activity, we synthesized 7 derivatives characterized by different lipophilicities. These

  通过将单克隆抗体与蓖麻毒蛋白的A链亚基偶联（RTA-IT），实现了定点毒素的递送。通过使用离子载体如莫能菌素，可以在体外显着提高RTA-IT的细胞杀伤力。为了降低莫能菌素的内在毒性并增强其体外和体内活性，我们合成了7种具有不同亲脂性的衍生物。还分析了这些衍生物的完整细胞离子活性，毒性和RTA-IT增强活性。在人白血病细胞系上测定了两种不同的RTA-IT。亲脂性，离子活性和RTA-IT增强之间存在相关性。具有最高极性电荷的化合物显示出较低的内在毒性，显示出适度的离子活性，并且仅在高浓度下才能增强RTA-IT，
• [4]Helicene-Squalene Fluorescent Nanoassemblies for Specific Targeting of Mitochondria in Live-Cell Imaging
  作者：Andrej Babič、Simon Pascal、Romain Duwald、Dimitri Moreau、Jérôme Lacour、Eric Allémann

  DOI：10.1002/adfm.201701839

  日期：2017.9

  electron microscope and cryogenic transmission electron microscope imaging that did not reveal higher order supramolecular structures. Investigations of their (chir)optical properties show red absorption maxima ≈600 nm and red fluorescence spanning up to the near‐infrared region, with average Stokes shifts of 1350–1550 cm−1. Live‐cell imaging by confocal microscopy reveals rapid internalization on the minute

  角鲨烯和阳离子二氮杂[4]螺旋烯1的酯，酰胺和直接连接的复合物易于制备。这些脂质染料构建体2，3和4给予在水介质中的单分散球形nanoassemblies周围100-130纳米的直径具有优良的稳定性数月。化合物2的外消旋和对映纯纳米组装件得到了充分表征，包括通过透射电子显微镜和低温透射电子显微镜成像，而这些成像都没有揭示高阶超分子结构。对它们的（手性）光学特性的研究表明，最大吸收峰≈600nm，红色荧光跨越近红外区域，平均斯托克斯位移为1350–1550 cm-1。通过共聚焦显微镜对活细胞成像显示出在微小的时间范围内的快速内在化和特定于细胞器的积累。与MitoTracker在几种癌细胞系中的共定位显示了[4]螺旋烯-角鲨烯纳米组装体对线粒体的特异性染色。据我们所知，这是基于角鲨烯的纳米组件靶向亚细胞的首次报道。
• A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer
  作者：Larissa Kotelevets、Eric Chastre、Joachim Caron、Julie Mougin、Gerard Bastian、Alain Pineau、Francine Walker、Therese Lehy、Didier Desmaële、Patrick Couvreur

  DOI：10.1158/0008-5472.can-16-1741

  日期：2017.6.1

  Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination. Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production, expression of heavy metal–inducible and stress-inducible genes, stress kinase cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis, oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue toxicity. Our results offer preclinical validation of a nanocarrier formulation that can safely improve chemotherapeutic efficacy, address risks of drug resistance, and improve patient compliance by enabling oral administration. Cancer Res; 77(11); 2964–75. ©2017 AACR.

  摘要 纳米技术为改善药物治疗（包括药物药理学）提供了多种可能性。目前的研究报告了一种简单的方法，即通过制作口服的装有顺铂的角鲨烯酰化纳米颗粒（SQ-CDDP NP）来提高顺铂治疗结肠癌的疗效。在人类结肠细胞和小鼠肠癌模型中评估了 SQ-CDDP NP 的细胞毒性作用。在细胞培养中，SQ-CDDP NP 的细胞毒性效力比未络合的顺铂至少高出 10 倍，这反映了细胞内蓄积和 DNA platination 的增强。机理研究表明，SQ-CDDP NP 可刺激 ROS 生成、重金属诱导基因和应激诱导基因的表达、应激激酶级联和细胞凋亡。在肠道肿瘤发生模型 ApcMin/+ 小鼠中，口服 SQ-CDDP NP 可抑制自发性肿瘤的形成和偶氮甲烷诱导的结肠癌发生，而且没有明显的组织毒性证据。我们的研究结果为一种纳米载体制剂提供了临床前验证，这种制剂可以安全地提高化疗效果，解决耐药性风险，并通过口服给药提高患者的依从性。Cancer Res; 77(11); 2964-75。©2017 AACR.
• Trisnorsqualene alcohol, a potent inhibitor of vertebrate squalene epoxidase
  作者：Stephanie E. Sen、Glenn D. Prestwich

  DOI：10.1021/ja00186a062

  日期：1989.2
• SEN, STEPHANIE E.;PRESTWICH, GLENN D., J. AMER. CHEM. SOC., 111,(1989) N, C. 1508-1510
  作者：SEN, STEPHANIE E.、PRESTWICH, GLENN D.

  DOI：——

  日期：——