cis,cis,trans-diamminedichloridobis(octanoato)platinum(IV) | 1447820-53-2

• 英文名称: cis,cis,trans-diamminedichloridobis(octanoato)platinum(IV)
• 英文别名: trans,cis,cis-[Pt(CH₃(CH₂)₆COO^-)₂Cl₂(NH₃)₂]
• CAS: 1447820-53-2
• 化学式: C₁₆H₃₆Cl₂N₂O₄Pt
• 分子量: 586.459
• InChiKey: CBEVNKQRYLYRAV-UHFFFAOYSA-J

计算性质

• 辛醇/水分配系数(LogP)：
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• 重原子数：
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• 可旋转键数：
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• 环数：
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• sp3杂化的碳原子比例：
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• 拓扑面积：
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• 氢给体数：
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• 氢受体数：
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反应信息

• 作为产物：
  描述：

  氧代铂 、 辛酰氯 以 N,N-二甲基甲酰胺 为溶剂， 生成 cis,cis,trans-diamminedichloridobis(octanoato)platinum(IV)
  参考文献：
  名称：

  一系列基于顺铂的脂族双（羧基）Pt（IV）前药的生物活性：有机链应持续多长时间？

  摘要：

  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

  DOI：

  10.1016/j.jinorgbio.2014.07.018

文献信息

• 一种同时载有siRNA和顺铂前药的新型酸敏纳米载体及其制备方法与应用
  申请人：中山大学孙逸仙纪念医院

  公开号：CN111000823A

  公开（公告）日：2020-04-14

  本发明公开了一种同时载有siRNA和顺铂前药的新型酸敏纳米载体及其制备方法与应用，所述制备方法先合成了一种易于转化、细胞内涵体pH响应的聚乙二醇‑b‑聚(2‑(二异丙基氨基)乙基甲基丙烯酸酯高分子材料，再利用该细胞内涵体pH响应的高分子材料构建新型酸敏纳米载体，用于同时输送siRNA和化疗前体药物。本发明所制备的纳米载体共输送siRNA和prodrug时，能够对内涵体的酸性pH做出响应，加快siRNA和prodrug的胞内释放，沉默化疗耐药相关的靶基因，并增加化疗敏感性，协同杀伤肿瘤细胞。
• Synthesis and characterization of cyclohexane-1<i>R</i>,2<i>R</i>-diamine-based Pt(<scp>iv</scp>) dicarboxylato anticancer prodrugs: their selective activity against human colon cancer cell lines
  作者：E. Gabano、M. Ravera、E. Perin、I. Zanellato、B. Rangone、M. J. McGlinchey、D. Osella

  DOI：10.1039/c8dt03950j

  日期：——

  diastereomers derived from the substitution of an equatorial chlorido ligand with a water molecule. The complexes have been tested on three different colon cancer cell lines having different histological history, and also on the cisplatin-sensitive A2780 ovarian cancer cell line for comparison. This allowed the evaluation not only of the increase in activity on passing from Pt(II) to Pt(IV) derivatives, but also

  从头合成或重新合成了三对基于顺铂和奥沙利铂样骨架的不对称二羧酸衍生物。轴向配体由一种中链脂肪酸（MCFA）组成，即clofibrate（即2-（p-氯苯氧基）-2-甲基丙酸（CA），庚酸酯（HA）或辛酸酯（OA），以及赋予此类缀合物可接受的水溶性的无活性乙酰基配体。稳定性测试为两种水解产物的部分形成提供了证据，这两种水解产物对应于两种赤水非对映异构体，它们是用水分子取代赤道氯代配体而得到的。已经在具有不同组织学历史的三种不同结肠癌细胞系上以及在顺铂敏感的A2780卵巢癌细胞系上测试了该复合物以进行比较。这样不仅可以评估从Pt（II）转变为Pt（IV）时活性的增加）衍生物，但也有环己烷-1 R，2 R-二胺载体配体对结肠癌细胞的选择性。
• 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.
• Antiproliferative activity of Pt(IV)-bis(carboxylato) conjugates on malignant pleural mesothelioma cells
  作者：Manuela Alessio、Ilaria Zanellato、Ilaria Bonarrigo、Elisabetta Gabano、Mauro Ravera、Domenico Osella

  DOI：10.1016/j.jinorgbio.2013.09.003

  日期：2013.12

  The bifunctional Pt(IV) conjugate cis,cis,trans-diamminedichloridobis(valproato)platinum(IV), based on the cisplatin square-plane with two axial valproato (2-propylpentanoate, VPA) ligands, has been re-synthesized with a modified procedure and its biological activity was compared with that of its isomer cis,cis,trans-diamminedichloridobis(n-octanoato)platinum(IV). Both complexes showed a striking cytotoxic effect (in the micro or sub-micromolar range) on various human carcinoma cell lines (namely ovarian, colon, breast and lung cancer), and, in particular, on cells derived from malignant pleural mesothelioma. This remarkable activity is due to the action of the cisplatin metabolite only, generated by the intracellular Pt(IV)-> Pt(II) reduction, which concentration is greatly increased by the enhanced cellular accumulation of the original, highly lipophilic Pt(IV)-bis(carboxylato) complexes. The two axial VPA ligands are released in a too low concentration to act as histone deacetylase inhibitor (HDACI), as VPA works in the millimolar range, so that no synergism can be claimed. Moreover, n-octanoic acid is substantially deprived of any HDACI propensity. (C) 2013 Elsevier Inc. All rights reserved.