cis,cis,trans-[Pt(NH₃)₂(Cl)₂(O₂C(CH₂)₃CH₃)₂] | 1103307-61-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: cis,cis,trans-[Pt(NH₃)₂(Cl)₂(O₂C(CH₂)₃CH₃)₂]
• 英文别名: Azane;hexanoate;platinum(4+);dichloride
• CAS: 1103307-61-4
• 化学式: C₁₂H₂₈Cl₂N₂O₄Pt
• 分子量: 530.351
• InChiKey: XVJZZXOHSRXRHG-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
  -5.04
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  82.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  cis,cis,trans-[Pt(NH₃)₂(Cl)₂(O₂C(CH₂)₃CH₃)₂] 在 NADH 、 FAD 作用下， 以 aq. phosphate buffer 为溶剂， 生成 cisplatin
  参考文献：
  名称：

  FAD 和黄素蛋白对铂和钌抗癌复合物的生物正交催化活化。

  摘要：

  生物正交催化的最新进展有望提供新的化学工具，用于在复杂的生物环境中进行化学选择性转化。在此，我们报道了 FAD（黄素腺嘌呤二核苷酸）、FMN（黄素单核苷酸）和四种黄素蛋白如何充当非常规光催化剂，能够将 PtIV 和 RuII 复合物转化为潜在有毒的 PtII 或 RuII -OH2 物质。在电子供体和低剂量可见光存在的情况下，黄素蛋白迷你单线态氧发生器 (miniSOG) 和 NADH 氧化酶 (NOX) 以生物正交选择性催化激活 PtIV 前药。在 NADH 存在的情况下，NOX 也在黑暗中催化 PtIV 活化，这首次表明黄素酶可能有助于启动 PtIV 化疗药物的活性。

  DOI：

  10.1002/anie.201800288
• 作为产物：
  描述：

  氧代铂 、 己酸酐 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以60%的产率得到cis,cis,trans-[Pt(NH₃)₂(Cl)₂(O₂C(CH₂)₃CH₃)₂]
  参考文献：
  名称：

  重新编程轴向配体可促进铂（iv）前药的自组装：克服耐药性并更安全地体内递送顺铂†

  摘要：

  我们在本文中对铂（IV）前药的轴向配体进行了重新编程，使所构建的前药实体具有在水溶液中自组装的能力。用Pluronic表面活性剂进一步掩盖PEG链使得这种纳米组件（称为Pt（IV）-NP）适合全身注射。值得注意的是，Pt（IV）-NP显着减轻了母体顺铂药物在体内的毒性，同时保留了药理活性。

  DOI：

  10.1039/c8cc03763a

文献信息

• 顺铂药物前体、制备方法和应用
  申请人：浙江大学

  公开号：CN109021026B

  公开（公告）日：2021-04-02

  本发明公开了一种顺铂药物前体、制备方法和应用，所述顺铂药物前体的结构式如式(I)，是由活化过的二羟基顺铂与疏水性分子发生酯化反应生成的。纳米制剂的表征通过动态光散射以及透射电子显微镜表明本发明中的纳米粒分布均匀，约30nm；体外细胞毒性实验中表明该纳米药物能够显著抑制肿瘤细胞(A549和LoVo)的增值；体内实验表明，相比顺铂注射液，在降低了系统毒性的基础上，具有抑制非小细胞肺癌A549皮下瘤的效果，具备良好的市场前景与临床应用价值。
• Biodegradable and pH-Responsive Acetalated Dextran (Ac-Dex) Nanoparticles for NIR Imaging and Controlled Delivery of a Platinum-Based Prodrug into Cancer Cells
  作者：Carolyne B. Braga、Gabriel Perli、Tiago B. Becher、Catia Ornelas

  DOI：10.1021/acs.molpharmaceut.9b00058

  日期：2019.5.6

  encapsulation efficiency, high stability in physiological conditions, and pH responsiveness. Drug-release studies clearly showed that the PtIV prodrug 3 release from Ac-Dex NPs was negligible at pH 7.4, whereas at pH 5.5, this compound was completely released with a controlled rate. Confocal laser scanning microscopy unambiguously showed that the NIR-dye 9/Ac-Dex NPs were efficiently taken up by MCF-7 cells

  基于可生物降解的乙缩醛葡聚糖聚合物（Ac-Dex）的纳米颗粒（NPs）用于近红外（NIR）成像，并控制Pt IV前药向癌细胞的递送。载有疏水性Pt IV前药3（Pt IV / Ac-Dex NPs）和新型疏水性NIR荧光染料9（NIR染料9）的Ac-Dex NP/ Ac-Dex NPs，以及与两种化合物共载的Ac-Dex NP（共载Ac-Dex NP），是使用一种水包油纳米乳液方法组装而成的。动态光散射测量和扫描电子显微镜图像显示，所得Ac-Dex NP是球形的，平均直径为100 nm，它通过增强的渗透和保留效果而适合在肿瘤中蓄积。新的纳米系统显示出高载药能力，高包封效率，在生理条件下的高稳定性和pH响应性。药物释放研究清楚地表明，Pt IV前药3在pH 7.4时，Ac-Dex NPs的释放可忽略不计，而在pH 5.5时，该化合物以受控的速率完全释放。共聚焦激光扫描显微镜清楚地表明，NIR-dye
• Biological activity of a series of cisplatin-based aliphatic bis(carboxylato) Pt(IV) prodrugs: How long the organic chain should be?
  作者：Ilaria Zanellato、Ilaria Bonarrigo、Donato Colangelo、Elisabetta Gabano、Mauro Ravera、Manuela Alessio、Domenico Osella

  DOI：10.1016/j.jinorgbio.2014.07.018

  日期：2014.11

  The biological properties of a series of cisplatin-based Pt(IV) prodrug candidates, namely trans,cis,cis-[Pt(carboxylato)2Cl2(NH3)2], where carboxylato = CH3(CH2)nCOO− [(1), n = 0; (2), n = 2; (3), n = 4; (4), n = 6] having a large interval of lipophilicity are discussed. The stability of the complexes was tested in different pH conditions (i.e. from 1.0 to 9.0) to simulate the hypothetical conditions

  一系列基于顺铂的Pt（IV）前药候选物的生物学特性，即反式，顺式，顺式-[Pt（羧基）2 Cl 2（NH 3）2 ]，其中羧基= CH 3（CH 2）n COO − [（1），n = 0; （2），n = 2; （3），n ＝ 4；（4），n ＝ 6]讨论了具有大的亲脂性间隔。配合物的稳定性在不同的pH条件下进行了测试（即（从1.0到9.0），以模拟口服给药的假设条件，显示出较高的稳定性（> 90％）。在抗坏血酸的存在下证明了向其活性Pt（II）代谢物的转化，具有拟一级动力学，其半衰期随着羧酸链长的增加而平稳降低。他们的抗增殖活性已在一大批人类癌细胞系中进行了体外评估。正如预期的那样，效力随着链长的增加而增加：3和4分别在大约一两个数量级的所有细胞系上比顺铂具有更高的活性。与非肿瘤细胞相比，两种复合物在顺铂耐药细胞系上也都保持了活性，并且显示出选择性的逐步提高。对多细胞肿瘤球体（MCTSs
• Combinatorial-Designed Epidermal Growth Factor Receptor-Targeted Chitosan Nanoparticles for Encapsulation and Delivery of Lipid-Modified Platinum Derivatives in Wild-Type and Resistant Non-Small-Cell Lung Cancer Cells
  作者：Ana Vanessa Nascimento、Amit Singh、Hassan Bousbaa、Domingos Ferreira、Bruno Sarmento、Mansoor M. Amiji

  DOI：10.1021/acs.molpharmaceut.5b00642

  日期：2015.12.7

  Development of efficient and versatile drug delivery platforms to overcome the physical and biological challenges in cancer therapeutics is an area of great interest, and novel materials are actively sought for such applications. Recent strides in polymer science have led to a combinatorial approach for generating a library of materials with different functional identities that can be "mixed and matched" to attain desired characteristics of a delivery vector. We have applied the combinatorial design to chitosan (CS), where the polymer backbone has been modified with polyethylene glycol, epidermal growth factor receptor-binding peptide, and lipid derivatives of varying chain length to encapsulate hydrophobic drugs. Cisplatin, cis-([PtCl2(NH3)(2)]), is one of the most potent chemotherapy drugs broadly administered for cancer treatment. Cisplatin is a hydrophilic drug, and in order for it to be encapsulated in the developed nanosystems, it was modified with lipids of varying chain length. The library of four CS derivatives and six platinum derivatives was self-assembled in aqueous medium and evaluated for physicochemical characteristics and cytotoxic effects in platinum-sensitive and -resistant lung cancer cells. The results show that the lipid-modified platinate encapsulation into CS nanoparticles significantly improved cellular cytotoxicity of the drug. In this work, we have also reinforced the idea that CS is a multifaceted system that can be as successful in delivering small molecules as it has been as a nucleic acids carrier.
• The Effect of Ligand Lipophilicity on the Nanoparticle Encapsulation of Pt(IV) Prodrugs
  作者：Timothy C. Johnstone、Stephen J. Lippard

  DOI：10.1021/ic4010642

  日期：2013.9.3

  In an effort to expand the therapeutic range of platinum anticancer agents, several new approaches to platinum-based therapy, including nanodelivery, are under active investigation. To better understand the effect of ligand lipophilicity on the encapsulation of Pt(IV) prodrugs within polymer nanoparticles, the series of compounds cis,cis,trans-[Pt(NH3)(2)Cl2L2] was prepared, where L. acetate, propanoate, butanoate, pentanoate, hexanoate, heptanoate, octanoate, nonanoate, and decanoate. The " lipophilicities of these compounds, assessed by reversed-phase HPLC, correlate with the octanol/water partition coefficients of their respective free carboxylic acid ligands, which in turn affect the degree of encapsulation of the ", Pt(IV) complex within the hydrophobic core of poly(lactic-co-glycolic acid)Wock-poly(ethylene glycol) (PLGA-PEG-COOH) nanoparticles. The most " lipophilic compound investigated, cis,cis,trans-[Pt(NH3)(2)Cl-2(O2C-(CH2)8CH(3))(2)], displayed the best encapsulation. This compound was therefore selected to evaluate the effect of increased platinum concentration on encapsulation. As the platinum concentration was increased, there was an initial increase in encapsulation followed by a decrease due to macroscopic precipitation. Maximal loading occurred when the platinum complex was present at a 40% w/w ratio with respect to polymer during the nanoprecipitation step. Particles formed under these optimal conditions had diameters of approximately 50 nm, as determined by transmission electron microscopy.