N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine | 1097907-11-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine
• 英文别名: N-(2-hydroxybenzyl)-N,N′-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine；N,N’-bis-(2-(N-methylimidazolyl)-methyl)-N(2-hydroxybenzyl)-1ethane-1,2-diamine；N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethene-1,2-diamine；2-[[(1-Methylimidazol-2-yl)methyl-[2-[(1-methylimidazol-2-yl)methylamino]ethyl]amino]methyl]phenol；2-[[(1-methylimidazol-2-yl)methyl-[2-[(1-methylimidazol-2-yl)methylamino]ethyl]amino]methyl]phenol
• CAS: 1097907-11-3
• 化学式: C₁₉H₂₆N₆O
• 分子量: 354.455
• InChiKey: QVRMNSHRXZTRQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine 、 2-(1-(6-hexanal)-1H-1,2,3-triazol-4-yl)pyridine chlorotricarbonylrhenium 在 三乙胺 、 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 以26%的产率得到
  参考文献：
  名称：

  细胞内位置很重要：合理的锰（ii）超氧化物歧化酶模拟复合物的抗炎活性。

  摘要：

  在氧化应激的细胞模型中研究了基于Mn的超氧化物歧化酶模拟物与基于Re的多峰探针的缀合物。使用Re和Mn X荧光研究了其形态。有趣的是，显示出不同于其未结合的类似物的分布，但是线粒体中的浓度相似且生物活性相似。

  DOI：

  10.1039/d0cc03398g
• 作为产物：
  描述：

  2-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]imidazolidine 在 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以100%的产率得到N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine
  参考文献：
  名称：

  一种新的五齿配体形成双核和单核 MnII 复合物：电化学、光谱和超氧化物歧化酶活性研究

  摘要：

  双核配合物 [1(PF6)2] 的 X 射线晶体结构来自一种新的配体，同时含有咪唑和苯酚部分，即 N-(2-羟基苄基)-N,N'-双 [2-(N-描述了甲基咪唑基）甲基]乙烷-1,2-二胺（LH），并研究了其在有机溶剂（CH3CN）中的性质（EPR，电化学）。[1(PF6)2] 在水溶液中显示为单核 MnII 物质，并显示出有效的 SOD 样活性，如在常规磷酸盐缓冲液和非配位缓冲液 (PIPES) 中进行的 McCord-Fridovich 测定所测量的那样。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

  DOI：

  10.1002/ejic.200601236

文献信息

• Anti-inflammatory activity of superoxide dismutase mimics functionalized with cell-penetrating peptides
  作者：Emilie Mathieu、Anne-Sophie Bernard、H. Y. Vincent Ching、Andrea Somogyi、Kadda Medjoubi、Jennifer Rodon Fores、Hélène C. Bertrand、Amandine Vincent、Sylvain Trépout、Jean-Luc Guerquin-Kern、Andreas Scheitler、Ivana Ivanović-Burmazović、Philippe Seksik、Nicolas Delsuc、Clotilde Policar

  DOI：10.1039/c9dt04619d

  日期：——

  A superoxide dismutase mimic (Mn1) was functionalized with three positively charged-peptides: RRRRRRRRR (Mn1-R9), RRWWWRRWRR (Mn1-RW9) or Fx-r-Fx-K (Mn1-MPP). Characterization of the physico-chemical properties of the complexes show that they share similar binding affinity for Mn2+, apparent reduction potential and intrinsic superoxide dismutase activity. However, their accumulation in cells is different

  超氧化物歧化酶模拟物（Mn1）用三个带正电荷的肽功能化：RRRRRRRRRR（Mn1-R9），RRWWWRRWRR（Mn1-RW9）或Fx-r-Fx-K（Mn1-MPP）。配合物的理化性质的表征表明，它们对Mn2 +具有相似的结合亲和力，表观还原电位和固有的超氧化物歧化酶活性。但是，它们在细胞中的积累及其亚细胞分布是不同的（Mn1-R9
• A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able To Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases
  作者：Emilie Mathieu、Anne-Sophie Bernard、Nicolas Delsuc、Elodie Quévrain、Géraldine Gazzah、Barry Lai、Florian Chain、Philippe Langella、Maria Bachelet、Joelle Masliah、Philippe Seksik、Clotilde Policar

  DOI：10.1021/acs.inorgchem.6b02695

  日期：2017.3.6

  chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial

  无机复合物越来越多地用于生物学和医学应用，金属药物的细胞渗透和分布问题对于理解其生物活性至关重要。已知氧化应激与炎症和抗氧化防御能力减弱的炎症性肠疾病有关。我们在这里报告了锰络合物Mn1模仿超氧化物歧化酶（SOD）的研究，该蛋白质参与了细胞抗氧化应激的保护作用，采用了一种结合无机Mn1的研究方法的无机细胞化学方法使用质谱进行细胞内形态分析，以及利用电子顺磁共振和空间分辨X射线荧光对其生物活性进行定量和分布。更准确地说，我们寻找并发现了细胞裂解物中Mn1的MS标记，并对总锰含量进行了定量。将细菌脂多糖激活的肠上皮细胞作为氧化应激和炎症的细胞模型。DNBS诱导的小鼠结肠炎用于研究Mn1的体内活性。Mn1发挥细胞内抗炎活性，至少保持部分协同作用，在整个细胞中弥散分布，并在功能上补充线粒体MnSOD。
• Deciphering the Metal Speciation in Low‐Molecular‐Weight Complexes by IMS‐MS: Application to the Detection of Manganese Superoxide Dismutase Mimics in Cell Lysates
  作者：Martha Zoumpoulaki、Gabrielle Schanne、Nicolas Delsuc、Hugues Preud'homme、Elodie Quévrain、Nicolas Eskenazi、Géraldine Gazzah、Regis Guillot、Philippe Seksik、Joelle Vinh、Ryszard Lobinski、Clotilde Policar

  DOI：10.1002/anie.202203066

  日期：2022.9.19

  Ion mobility spectrometry (IMS) effectively distinguishes between first-row divalent transition metal complexes, despite very similar ionic radii of the ions. The speciation study of two Mn-based superoxide dismutase (SOD) mimetics (or mimics) was performed in intricate cell lysates using IMS coupled to mass spectrometry (IMS-MS). Quantification was performed by comparison with a standard consisting

  尽管离子的离子半径非常相似，但离子迁移谱 (IMS) 可以有效区分第一行二价过渡金属配合物。两种基于锰的超氧化物歧化酶 (SOD) 模拟物（或模拟物）的物种形成研究是使用 IMS 耦合质谱法 (IMS-MS) 在复杂的细胞裂解物中进行的。通过与由类似的13 C 6 -Co II重配体组成的标准进行比较来进行定量。
• A New Manganese Superoxide Dismutase Mimetic Improves Oxaliplatin-Induced Neuropathy and Global Tolerance in Mice
  作者：Caroline Prieux-Klotz、Henri Chédotal、Martha Zoumpoulaki、Sandrine Chouzenoux、Charlotte Chêne、Alvaro Lopez-Sanchez、Marine Thomas、Priya Ranjan Sahoo、Clotilde Policar、Frédéric Batteux、Hélène C. Bertrand、Carole Nicco、Romain Coriat

  DOI：10.3390/ijms232112938

  日期：——

  Reactive oxygen species (ROS) are produced by every aerobic cell during mitochondrial oxidative metabolism as well as in cellular response to xenobiotics, cytokines, and bacterial invasion. Superoxide Dismutases (SOD) are antioxidant proteins that convert superoxide anions (O2•−) to hydrogen peroxide (H2O2) and dioxygen. Using the differential in the level of oxidative stress between normal and cancer cells, SOD mimetics can show an antitumoral effect and prevent oxaliplatin-induced peripheral neuropathy. New Pt(IV) conjugate prodrugs (OxPt-x-Mn1C1A (x = 1, 1-OH, 2)), combining oxaliplatin and a Mn SOD mimic (MnSODm Mn1C1A) with a covalent link, were designed. Their stability in buffer and in the presence of sodium ascorbate was studied. In vitro, their antitumoral activity was assessed by the viability and ROS production of tumor cell lines (CT16, HCT 116, KC) and fibroblasts (primary culture and NIH 3T3). In vivo, a murine model of colorectal cancer was created with subcutaneous injection of CT26 cells in Balb/c mice. Tumor size and volume were measured weekly in four groups: vehicle, oxaliplatin, and oxaliplatin associated with MnSODm Mn1C1A and the bis-conjugate OxPt-2-Mn1C1A. Oxaliplatin-induced peripheral neuropathy (OIPN) was assessed using a Von Frey test reflecting chronic hypoalgesia. Tolerance to treatment was assessed with a clinical score including four items: weight loss, weariness, alopecia, and diarrhea. In vitro, Mn1C1A associated with oxaliplatin and Pt(IV) conjugates treatment induced significantly higher production of H2O2 in all cell lines and showed a significant improvement of the antitumoral efficacy compared to oxaliplatin alone. In vivo, the association of Mn1C1A to oxaliplatin did not decrease its antitumoral activity, while OxPt-2-Mn1C1A had lower antitumoral activity than oxaliplatin alone. Mn1C1A associated with oxaliplatin significantly decreased OIPN and also improved global clinical tolerance of oxaliplatin. A neuroprotective effect was observed, associated with a significantly improved tolerance to oxaliplatin without impairing its antitumoral activity.

  每个有氧细胞在线粒体氧化代谢过程中，以及在细胞对异种生物、细胞因子和细菌入侵的反应过程中，都会产生活性氧（ROS）。超氧化物歧化酶（SOD）是一种抗氧化蛋白，可将超氧阴离子（O2--）转化为过氧化氢（H2O2）和二氧。利用正常细胞和癌细胞之间氧化应激水平的差异，SOD模拟物可以显示抗肿瘤效果，并预防奥沙利铂诱发的周围神经病变。本研究设计了新的铂(IV)共轭原药（OxPt-x-Mn1C1A (x = 1, 1-OH, 2)），将奥沙利铂和锰SOD模拟物（MnSODm Mn1C1A）通过共价键结合在一起。研究了它们在缓冲液和抗坏血酸钠存在下的稳定性。在体外，通过肿瘤细胞系（CT16、HCT 116、KC）和成纤维细胞（原代培养和 NIH 3T3）的存活率和 ROS 生成来评估它们的抗肿瘤活性。在体内，通过向 Balb/c 小鼠皮下注射 CT26 细胞，建立了小鼠结直肠癌模型。每周测量四组小鼠的肿瘤大小和体积：载体组、奥沙利铂组、奥沙利铂与 MnSODm Mn1C1A 和双结合剂 OxPt-2-Mn1C1A 组。奥沙利铂诱导的周围神经病变（OIPN）是通过反映慢性痛觉减退的 Von Frey 试验进行评估的。对治疗耐受性的评估采用临床评分法，包括四个项目：体重下降、倦怠、脱发和腹泻。在体外，Mn1C1A 与奥沙利铂和铂(IV)共轭物联合治疗可诱导所有细胞株产生更多的 H2O2，与单独使用奥沙利铂相比，抗肿瘤疗效显著提高。在体内，Mn1C1A 与奥沙利铂的结合不会降低其抗肿瘤活性，而 OxPt-2-Mn1C1A 的抗肿瘤活性低于单独使用奥沙利铂。与奥沙利铂联用的 Mn1C1A 能显著降低 OIPN，还能改善奥沙利铂的总体临床耐受性。观察到的神经保护效应与奥沙利铂耐受性的明显改善有关，但并不影响其抗肿瘤活性。
• Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides
  作者：H.Y. Vincent Ching、Isabell Kenkel、Nicolas Delsuc、Emilie Mathieu、Ivana Ivanović-Burmazović、Clotilde Policar

  DOI：10.1016/j.jinorgbio.2016.01.025

  日期：2016.7

  Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL](+) (where HL = N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyllethane-1,2-diamine), namely [MnL'-Arg((n - 1))](n+) (where n = 2, 4, 7 and 10) and [MnL'-Gly(1)](+)center dot[MnL'-Arg((n) (-) (1))](n+) contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to Mn-II with association constants (K-assoc) between 1.6 and 3.3 x 10(6) M-1. The Mn-III/Mn-II redox potential of the conjugates was between 0.27 and 0.30 V vs SCE, slightly higher than [MnL](+) under the same conditions, but remain at a value that facilitates O-2(center dot-) dismutation. The catalytic rate constant (k(cat)) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL](+) (k(cat) = 5.0 +/- 0.1 x 10(6) M-1 s(-1)) led to a lower value (i.e. for [MnL'Gly](+), k(cat) = 4.2 +/- 0.1 x 10(6) M-1 s(-1)) However, under the same conditions, k(cat) values between 5.0 +/- 0.4 x 10(6) M-1 s(-1) and 6.6 +/- 0.1 x 10(6) M-1 s(-1) were determined for [MnL'-Arg((n - 1))](n+) conjugates, indicating that the cationic residue(s) compensated for the loss in activity. Analysis of the effect of ionic strength on the k(cat) strongly suggested that not all the charges were involved, but only the closest ones electrostatically influenced the SOD active metal centre. (C) 2016 Published by Elsevier Inc.