20-O-(6-azidohexanoyl)camptothecin | 924279-35-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: 20-O-(6-azidohexanoyl)camptothecin
• 英文别名: [(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] 6-azidohexanoate
• CAS: 924279-35-6
• 化学式: C₂₆H₂₅N₅O₅
• 分子量: 487.515
• InChiKey: SLZFQYCZAZKEAH-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  sodium prop-2-yne-1-sulfonate 、 20-O-(6-azidohexanoyl)camptothecin 在 sodium ascorbate 、 copper(II) sulfate 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 2.0h， 以55%的产率得到sodium;[1-[6-[[(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl]oxy]-6-oxohexyl]triazol-4-yl]methanesulfonate
  参考文献：
  名称：

  Sulfonates-PMMA nanoparticles conjugates: A versatile system for multimodal application

  摘要：

  We report herein the viability of a novel nanoparticles (NPs) conjugated system, namely the attachment, based on ionic and hydrophobic interactions, of different sulfonated organic salts to positively charged poly(methylmethacrylate) (PMMA)-based core-shell nanoparticles (EA0) having an high density of ammonium groups on their shells. In this context three different applications of the sulfonates@EA0 systems have been described. In detail, their ability as cytotoxic drugs and pro-drugs carriers was evaluated in vitro on NCI-H460 cell line and in vivo against human ovarian carcinoma IGROV-1 cells. Besides, 8-hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt (HPTS) was chosen for NPs loading, and its internalization as bioimaging probe was evaluated on Hep G2 cells. Overall, the available data support the interest for these PMMA NPs@sulfonates systems as a promising formulation for theranostic applications. In vivo biological data strongly support the potential value of these core-shell NPs as delivery system for negatively charged drugs or biologically active molecules. Additionally, we have demonstrated the ability of these PMMA core-shell nanoparticles to act as efficient carriers of fluorophores. In principle, thanks to the high PMMA NPs external charge density, sequential and very easy post-loading of different sulfonates is achievable, thus allowing the preparation of nanocarriers either with bi-modal drug delivery behaviour or as theranostic systems. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.023
• 作为产物：
  描述：

  6-溴己酸甲酯 在 4-二甲氨基吡啶 、 sodium azide 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 55.0h， 生成 20-O-(6-azidohexanoyl)camptothecin
  参考文献：
  名称：

  CLICKABLE POLYOXETANE CARRIER FOR DRUG DELIVERY

  摘要：

  提供一种聚合物，包括具有以下公式的亚单位：(I)，其中A、B、C、D、a、b、c、d和p在此定义。提供了组成物、制备方法和使用方法。

  公开号：

  US20150258204A1

文献信息

• ZWITTERIONIC POLYMERS WITH THERAPEUTIC MOIETIES
  申请人：University of Massachusetts

  公开号：US20160346400A1

  公开（公告）日：2016-12-01

  The invention generally relates to zwitterionic polymers (including zwitterionic copolymers), such as polymethacrylic structures, with pendent functional moieties, such as therapeutic or biologic moieties. More particularly, the invention relates to phosphorylcholine-substituted methacrylic polymers prepared by free radical polymerization and click chemistry, for example, and compositions and products comprising same, as well as related methods and uses of the compositions, for example, as biological or therapeutic agents and in drug delivery thereof.

  这项发明通常涉及带有侧链功能基团的带电离子聚合物（包括带电离子共聚物），例如聚甲基丙烯酸结构，其中功能基团为治疗或生物学基团。更具体地，该发明涉及通过自由基聚合和点击化学制备的磷酰胆碱取代的甲基丙烯酸聚合物，以及包括同样的组合物和产品，以及相关方法和使用这些组合物，例如作为生物学或治疗剂以及药物递送的用途。
• The Sequence-Specific Cellular Uptake of Spherical Nucleic Acid Nanoparticle Conjugates
  作者：Suguna P. Narayan、Chung Hang J. Choi、Liangliang Hao、Colin M. Calabrese、Evelyn Auyeung、Chuan Zhang、Olga J. G. M. Goor、Chad A. Mirkin

  DOI：10.1002/smll.201500027

  日期：2015.9

  The sequence‐dependent cellular uptake of spherical nucleic acid nanoparticle conjugates (SNAs) is investigated. This process occurs by interaction with class A scavenger receptors (SR‐A) and caveolae‐mediated endocytosis. It is known that linear poly(guanine) (poly G) is a natural ligand for SR‐A, and it has been proposed that interaction of poly G with SR‐A is dependent on the formation of G‐quadruplexes

  研究了球形核酸纳米颗粒偶联物（SNA）的序列依赖性细胞摄取。该过程是通过与A类清除剂受体（SR‐A）和小窝介导的内吞作用相互作用而发生的。已知线性聚鸟嘌呤（poly G）是SR‐A的天然配体，有人提出poly G与SR‐A的相互作用取决于G‐四链体的形成。由于已知富含G的寡核苷酸会与SR‐A强烈相互作用，因此假设具有较高G含量的SNA能够比由其他核苷酸组成的SNA进入细胞的数量更大，因此可以测量SNA的细胞内在化作为组成寡核苷酸序列的函数。实际上，具有丰富G含量的SNA显示出最高的细胞吸收率。使用这个假设，将一个小分子（喜树碱）与SNA化学偶联以形成药物-SNA偶联物，并且发现聚G SNA将喜树碱递送至细胞的最多，并在癌细胞中具有最高的细胞毒性。我们的数据阐明了增强球形核酸细胞内递送的重要设计考虑因素。
• Formation of nanoparticles by cooperative inclusion between (<i>S</i>)-camptothecin-modified dextrans and β-cyclodextrin polymers
  作者：Thorbjørn Terndrup Nielsen、Catherine Amiel、Laurent Duroux、Kim Lambertsen Larsen、Lars Wagner Städe、Reinhard Wimmer、Véronique Wintgens

  DOI：10.3762/bjoc.11.14

  日期：——

  Novel (S)-camptothecin–dextran polymers were obtained by “click” grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were prepared with a degree of substitution of (S)-camptothecin between 3.1 and 10.2%. The binding properties with β-cyclodextrin and β-cyclodextrin polymers were measured by isothermal titration calorimetry and fluorescence spectroscopy, showing no binding with β-cyclodextrin but high binding with β-cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin–dextran polymers and the β-cyclodextrin polymers.

  小说（S）-喜树碱-葡聚糖聚合物是通过对带有偶氮修饰的（S）-喜树碱和炔烃修饰的葡聚糖进行“点击”嫁接得到的。基于分别为10 kDa和70 kDa的葡聚糖制备了两个系列，其（S）-喜树碱的取代度在3.1%至10.2%之间。通过等温滴定热量计和荧光光谱法测量了与β-环糊精和β-环糊精聚合物的结合性能，结果显示与β-环糊精无结合，但与β-环糊精聚合物有很高的结合性。在水溶液中，（S）-喜树碱-葡聚糖聚合物与β-环糊精聚合物之间形成了纳米粒子。
• A Clickable and Photocleavable Lipid Analogue for Cell Membrane Delivery and Release
  作者：Shahrina Alam、Daiane S. Alves、Stuart A. Whitehead、Andrew M. Bayer、Christopher D. McNitt、Vladimir V. Popik、Francisco N. Barrera、Michael D. Best

  DOI：10.1021/acs.bioconjchem.5b00044

  日期：2015.6.17

  For drug delivery purposes, the ability to conveniently attach a targeting moiety that will deliver drugs to cells and then enable controlled release of the active molecule after localization is desirable. Toward this end, we designed and synthesized clickable and photocleavable lipid analogue 1 to maximize the efficiency of bioconjugation and triggered release. This compound contains a dibenzocyclooctyne group for bioorthogonal derivatization linked via a photocleavable 2-nitrobenzyl moiety at the headgroup of a synthetic lipid backbone for targeting to cell membranes. To assess delivery and release using this system, we report fluorescence-based assays for liposomal modification and photocleavage in solution as well as through surface immobilization to demonstrate successful liposome functionalization and photoinduced release. In addition, fluorophore delivery to and release from live cells was confirmed and characterized using fluorescence microscopy and flow cytometry analysis in which 1 was delivered to cells, derivatized, and photocleaved. Finally, drug delivery studies were performed using an azide-tagged analogue of camptothecin, a potent anticancer drug that is challenging to deliver due to poor solubility. In this case, the ester attachment of the azide tag acted as a caging group for release by intracellular esterases rather than through photocleavage. This resulted in a dose-dependent response in the presence of liposomes containing delivery agent 1, confirming the ability of this compound to stimulate delivery to the cytoplasm of cells.

  为了实现药物递送的目的，能够方便地附加一个靶向部分，将药物递送至细胞，并在定位后实现活性分子的可控释放，这是可取的。为此，我们设计并合成了可点击且光裂解的脂质类似物1，以最大限度地提高生物共轭和触发释放的效率。该化合物包含一个通过光裂解的2-硝基苄基部分连接的二苯并环辛炔基团，位于合成脂质骨架的头部，用于靶向细胞膜。为了评估该系统的递送和释放，我们报道了基于荧光的脂质体修饰和溶液中以及通过表面固定化的光裂解实验，以证明成功实现脂质体功能化和光诱导释放的证据。此外，通过荧光显微镜和流式细胞术分析确认并表征了荧光团向活细胞的递送和释放，其中1被递送至细胞、衍生化并光裂解。最后，使用了一种带有叠氮标记的喜树碱类似物进行药物递送研究，喜树碱是一种具有强抗癌活性的药物，但由于其溶解性差而难以递送。在这种情况下，叠氮标签的酯键连接起到了笼蔽基团的作用，通过细胞内酯酶的释放而不是光裂解。结果显示，在含有递送剂1的脂质体存在下，剂量依赖性响应得到了确认，证实了该化合物刺激细胞质内部递送的能力。
• Synthesis of Water-Soluble Camptothecin–Polyoxetane Conjugates via Click Chemistry
  作者：Olga Yu. Zolotarskaya、Alison F. Wagner、Jason M. Beckta、Kristoffer Valerie、Kenneth J. Wynne、Hu Yang

  DOI：10.1021/mp3005066

  日期：2012.11.5

  were synthesized using a clickable polymeric platform P(EAMO) that was made by polymerization of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (i.e., EAMO). CPT was first modified with a linker 6-azidohexanoic acid via an ester linkage to yield CPT-azide. CPT-azide was then click coupled to P(EAMO) in dichloromethane using bromotris(triphenylphosphine)copper(I)/N,N-diisopropylethylamine. For

  水溶性喜树碱 (CPT)-聚氧杂环丁烷偶联物使用可点击聚合平台 P(EAMO) 合成，该平台通过乙炔官能化 3-乙基-3-（羟甲基）氧杂环丁烷（即 EAMO）聚合制成。CPT 首先通过酯键用接头 6-叠氮己酸修饰，得到 CPT-叠氮化物。然后使用溴三(三苯基膦)铜(I)/ N，N-二异丙基乙胺在二氯甲烷中将CPT-叠氮化物点击偶联至P(EAMO) 。为了提高水溶性和细胞相容性，甲氧基聚乙二醇叠氮化物 (mPEG-叠氮化物) 由 mPEG 750 g mol –1合成，并使用硫酸铜 (II) 和抗坏血酸钠点击接枝到 P(EAMO)- g -CPT。1H NMR 光谱证实了所有中间体和最终产物 P(EAMO) -g- CPT/PEG 的合成。发现 CPT 保留了其治疗活性的内酯形式。所得的 P(EAMO) -g- CPT/PEG 偶联物是水溶性的，对人神经胶质瘤细胞产生剂量依赖性的细胞毒性，并增加