(2-hydroxy-1,3-diaminopropane-k²N,N’)dichloro platinum(II) | 35022-53-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2-hydroxy-1,3-diaminopropane-k²N,N’)dichloro platinum(II)
• 英文别名: (1,3-diamino-2-propanol-N,N')dichloroplatinum(II)；[PtCl₂(HO-pda)]；dichloro κN,N'-(1,3-diamino-2-propanol)platinum(II)
• CAS: 35022-53-8
• 化学式: C₃H₁₀Cl₂N₂OPt
• 分子量: 356.111
• InChiKey: JMFKCFYFOFWLOD-UHFFFAOYSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为反应物：
  描述：

  (2-hydroxy-1,3-diaminopropane-k²N,N’)dichloro platinum(II) 、 丙腈 在 盐酸 作用下， 以 水 为溶剂， 反应 2.0h， 以91%的产率得到
  参考文献：
  名称：

  Using a Build-and-Click Approach for Producing Structural and Functional Diversity in DNA-Targeted Hybrid Anticancer Agents

  摘要：

  An efficient screening method was developed for functionalized DNA targeted platinum-containing hybrid anticancer agents based on metal mediated amine-to-nitrile addition, a form of "click" chemistry. The goal of the study was in generate platinum-acridine agents for their use as cytotoxic "warheads" in targeted and multifunctional therapies. This was achieved by introducing hydroxl, carboxylic acid, and azide functionalities in the acridine linker moiety and by varying the nonleaving groups attached to platinum. The assay, which was based on microscale reactions between 6 platinum-nitrile complexes and 10 acridine derivatives, yielded a small library of 60 platinum-acridines. Reactions were monitored, and product mixtures were quantitatively analyzed by automated in-line high-performance liquid chromatography-electrospray mass spectrometry (LC-ESMS) analysis and subjected to cell viability screening using a nonradioactive cell proliferation assay. The new prescreening methodology proves to be a powerful tool for establishing structure-activity relationships and for identifying target compounds.

  DOI：

  10.1021/jm301278c
• 作为产物：
  描述：

  chloro κN,N′-(1,3-diamino 2-propanol) κS-dimethyl sulfoxide platinum(II) chloride 在 lithium chloride 作用下， 以 水 为溶剂， 反应 2.0h， 以26%的产率得到(2-hydroxy-1,3-diaminopropane-k²N,N’)dichloro platinum(II)
  参考文献：
  名称：

  含顺铂片段的卢潘型三萜衍生物的合成及抗癌性能的研究

  摘要：

  桦木酸1和顺铂都是有前途的抗肿瘤药物，可诱导癌细胞凋亡。在本研究中，合成了一系列新的桦木酸-顺铂结合物，并针对五种不同的肿瘤细胞系评估了细胞毒性和选择性。目的是结合与凋亡诱导有关的两个结构单元。衍生物在微摩尔浓度下发挥剂量依赖性的抗增殖作用，并研究和讨论了这些结构变异对抗癌活性的影响。几种化合物显示出显着的抗肿瘤活性，这是最活跃的物质3- O-乙酰贝丁酸（2-（2-氨基乙基）氨基乙基）酰胺（IC 50 = 1.30–2.24μM）。有趣的是，桦木酸-顺铂结合物的细胞毒性比前体低。

  DOI：

  10.1016/j.ejmech.2014.01.031

文献信息

• Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance
  作者：Wilma Neumann、Brenda C. Crews、Menyhárt B. Sárosi、Cristina M. Daniel、Kebreab Ghebreselasie、Matthias S. Scholz、Lawrence J. Marnett、Evamarie Hey-Hawkins

  DOI：10.1002/cmdc.201402353

  日期：2015.1

  against platinum‐based antitumor drugs. Cisplatin analogues were conjugated with COX inhibitors (indomethacin, ibuprofen) to study the synergistic effects that were previously observed in combination treatments. The conjugates ensure concerted transport of both drugs into cells, and subsequent intracellular cleavage enables a dual‐action mode. Whereas the platinum(II) complexes showed cytotoxicities similar

  环氧合酶 (COX) 是一种参与肿瘤发生的酶，与肿瘤细胞对铂类抗肿瘤药物的耐药性有关。顺铂类似物与 COX 抑制剂（吲哚美辛、布洛芬）结合以研究先前在联合治疗中观察到的协同作用。偶联物确保两种药物协同转运到细胞中，随后的细胞内裂解可实现双重作用模式。铂 (II) 配合物显示出与顺铂相似的细胞毒性，而铂 (IV) 偶联物​​显示出高度增加的细胞毒性活性，并能够完全克服顺铂相关的耐药性。尽管一些复合物是有效的 COX 抑制剂，但这些偶联物似乎通过不依赖于 COX 的机制发挥其细胞毒作用。反而，偶联物增加的亲脂性和动力学惰性似乎促进了铂类药物的细胞积累，从而提高了抗肿瘤剂的功效。这些偶联物是阐明 COX 抑制剂对肿瘤细胞中铂类抗癌药物的直接影响的重要工具。
• pH and thermo dual stimulus-responsive liposome nanoparticles for targeted delivery of platinum-acridine hybrid agent
  作者：Qian Zhou、Chaoqun You、Yang Ling、Hongshuai Wu、Baiwang Sun

  DOI：10.1016/j.lfs.2018.11.052

  日期：2019.1

  The complexes of the type [PtCl(L2)(ACRAMTU)](NO3)(2) (ACRAMTU=1-[2-(acridin-9-ylamino) ethyl]-1, 3-dimethylthiourea) were synthesized: PT-ACRAMTU (1), L2 = ethane-1,2- diamine (en); PT(dach)-ACRAMTU (2), L2 =(1R, 2R)-1, 2-diaminocyclohexane (dach); PT(pda-OH)-ACRAMTU (3), L2 = 2-hydroxy-1, 3-propanediamine (pda-OH). The complexes containing diverse diamines exhibit different DNA binding capacity and cytotoxicity. Complex 3 shows excellent capability not only on the strongest non-cisplatin-type DNA damage, but also superior anticancer activity in NCI-H460 cells (IC50 = 0.23 +/- 0.05 mu M). For overcoming water insolubly and side effects, we encapsulated complex 3 into liposomes. PT@NPs were characterized in terms of particle size, morphology, drug loading capacity (DLC), encapsulation efficiency (EE) and stability. In vitro triggered release showed that the release of the platinum drug was steerable and the release rate was fast under low pH (< 7.0) and high temperature (> T-m = 41 degrees C). PT@NPs showed significant inhibitory effect in NCI-H460 cells. Flow cytometry analysis indicates G0/G1 phase arrest of cells treated with complex 3, whereas cells treated with cisplatin progress to G2/M of the cell cycle. The mechanistic differences validate that complex 3 is a potent anticancer agent superior than current clinical platinum-based therapies. PT@NPs have the potential in drug delivery systems (DDS) for non-small cell lung cancer (NSCLC) therapy.
• Oksanen, Anneli; Kivekaes, Raikko; Lumme, Paavo, Acta Crystallographica, Section C: Crystal Structure Communications, 1991, vol. 47, p. 719 - 722
  作者：Oksanen, Anneli、Kivekaes, Raikko、Lumme, Paavo、Laitalainen, Tarja

  DOI：——

  日期：——
• Using a Build-and-Click Approach for Producing Structural and Functional Diversity in DNA-Targeted Hybrid Anticancer Agents
  作者：Song Ding、Xin Qiao、Gregory L. Kucera、Ulrich Bierbach

  DOI：10.1021/jm301278c

  日期：2012.11.26

  An efficient screening method was developed for functionalized DNA targeted platinum-containing hybrid anticancer agents based on metal mediated amine-to-nitrile addition, a form of "click" chemistry. The goal of the study was in generate platinum-acridine agents for their use as cytotoxic "warheads" in targeted and multifunctional therapies. This was achieved by introducing hydroxl, carboxylic acid, and azide functionalities in the acridine linker moiety and by varying the nonleaving groups attached to platinum. The assay, which was based on microscale reactions between 6 platinum-nitrile complexes and 10 acridine derivatives, yielded a small library of 60 platinum-acridines. Reactions were monitored, and product mixtures were quantitatively analyzed by automated in-line high-performance liquid chromatography-electrospray mass spectrometry (LC-ESMS) analysis and subjected to cell viability screening using a nonradioactive cell proliferation assay. The new prescreening methodology proves to be a powerful tool for establishing structure-activity relationships and for identifying target compounds.
• Synthesis and studies of anticancer properties of lupane-type triterpenoid derivatives containing a cisplatin fragment
  作者：Daniel Emmerich、Kranthi Vanchanagiri、Leopoldo C. Baratto、Harry Schmidt、Reinhard Paschke

  DOI：10.1016/j.ejmech.2014.01.031

  日期：2014.3

  against five different tumor cell lines. The aim was to combine two structural units, both related with apoptosis induction. The derivatives exerted a dose-dependent antiproliferative action at micromolar concentrations and the effect of these structural variations on anticancer activity was studied and discussed. Several compounds revealed significant antitumor activity, as the most active substance 3-O-acetylbetulinic

  桦木酸1和顺铂都是有前途的抗肿瘤药物，可诱导癌细胞凋亡。在本研究中，合成了一系列新的桦木酸-顺铂结合物，并针对五种不同的肿瘤细胞系评估了细胞毒性和选择性。目的是结合与凋亡诱导有关的两个结构单元。衍生物在微摩尔浓度下发挥剂量依赖性的抗增殖作用，并研究和讨论了这些结构变异对抗癌活性的影响。几种化合物显示出显着的抗肿瘤活性，这是最活跃的物质3- O-乙酰贝丁酸（2-（2-氨基乙基）氨基乙基）酰胺（IC 50 = 1.30–2.24μM）。有趣的是，桦木酸-顺铂结合物的细胞毒性比前体低。