2-iodohypericin

• 分子结构分类: 有机化合物 - 苯类化合物 - 芘
• 英文名称: 2-iodohypericin
• 英文别名: 5,7,11,18,22,24-hexahydroxy-6-iodo-13,16-dimethyloctacyclo[13.11.1.12,10.03,8.04,25.019,27.021,26.014,28]octacosa-1(27),2(28),3,5,7,10,12,14,16,18,21,23,25-tridecaene-9,20-dione
• 化学式: C₃₀H₁₅IO₈
• 分子量: 630.349
• InChiKey: QCZMLQMQBDQJPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.69
• 重原子数：
  39.0
• 可旋转键数：
  0.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  155.52
• 氢给体数：
  6.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  大黄素 在 吡啶 、 过氧乙酸 哌啶 、 吡啶-N-氧化物 、 盐酸 、 sodium hydroxide 、 磷酸 、 iron(II) sulfate 、 溶剂黄146 、 sodium iodide 、 tin(ll) chloride 作用下， 以 乙醇 、 水 、 丙酮 为溶剂， 反应 13.5h， 生成 2-iodohypericin
  参考文献：
  名称：

  Accumulation and Photocytotoxicity of Hypericin and Analogs in Two- and Three-Dimensional Cultures of Transitional Cell Carcinoma Cells¶

  摘要：

  The aim of this study was to investigate the in vitro cellular accumulation, distribution and photocytotoxic effect of hypericin in two-dimensional (2-D) and three-dimensional (3-D) cultured RT-112 transitional cell carcinoma cells of the bladder. In addition, two iodinated derivatives of hypericin were incorporated to investigate whether these analogs, with their increased lipophilicity and heavy-atom effect, display a different biological behavior and optimized photodynamic effect. The results indicate that hypericin and mono-iodohypericin behave similarly in terms of cellular accumulation, spheroidal distribution and photocytotoxic effect. In contrast, di-iodohypericin concentrated to a higher extent in monolayers and spheroids, but the accumulation was restricted to the outermost part of the spheroid. An inverse correlation therefore seems to exist between the extent of cellular uptake under 2-D conditions and the penetration of the compounds in multicellular systems. Moreover, a less pronounced photocytotoxic effect was observed for di-iodohypericin in both 2-D and 3-D cell culture systems. It can be concluded that iodinated derivatives of hypericin do not show an increased cytotoxic effect upon irradiation in either monolayers or spheroids. Moreover, this study shows that when new photosensitizers are preclinically developed, the use of 3-D cell aggregates is critical for a correct evaluation of their efficacy.

  DOI：

  10.1562/0031-8655(2003)078<0607:aapoha>2.0.co;2

文献信息

• Preparation, analysis and biodistribution in mice of iodine-123 labelled derivatives of hypericin
  作者：Guy Bormans、Dieter Huyghe、Annemie Christiaen、Kristin Verbeke、Tjibbe de Groot、Hubert Vanbilloen、Peter de Witte、Alfons Verbruggen

  DOI：10.1002/jlcr.812

  日期：2004.3.15

  The synthesis of iodine-123 labelled mono- and di-iodo derivatives of hypericin, an hydroxylated phenanthroperylenequinone which is used for photodynamic therapy and has been shown to accumulate in several tumour types, is reported. Labelling was performed by electrophilic substitution on hypericin or iodohypericin with [123I]iodide in the presence of peracetic acid and provided both mono-[123I]iodohypericin and di-[123I]iodohypericin in good radiochemical yields (>80%). Mono-[123I]iodohypericin was obtained with a high specific activity (925 GBq/μmol) whereas di-[123I]iodohypericin was obtained in low specific activity (4 GBq/μmol) due to deiodination and subsequent iodination of iodohypericin which occurred during the labelling reaction. Biodistribution studies in mice showed a slow blood clearance and extensive hepatobiliary clearance as well as faecal excretion for both compounds. They will be further evaluated with regard to their tumor seeking properties. Copyright © 2004 John Wiley & Sons, Ltd.

  报告了碘-123标记的单碘和二碘金丝桃素衍生物的合成，金丝桃素是一种羟基化菲呫醌，用于光动力疗法，并已证明可积聚在多种肿瘤中。标记是通过在过乙酸存在下，用[123I]碘化物对金丝桃素或碘化金丝桃素进行亲电取代反应而进行的，并提供了单[123I]碘化金丝桃素和二[123I]碘化金丝桃素，放射化学收率良好（>80%）。单[123I]碘化金丝桃素具有高比活度（925 GBq/μmol），而二[123I]碘化金丝桃素的比活度较低（4 GBq/μmol），这是由于在标记反应期间发生了碘化金丝桃素的脱碘和随后的碘化反应。在小鼠体内的生物分布研究表明，这两种化合物具有缓慢的血液清除和广泛的肝胆清除以及粪便排泄。将进一步评估它们寻找肿瘤的特性。版权 © 2004 John Wiley & Sons, Ltd.
• Accumulation and Photocytotoxicity of Hypericin and Analogs in Two- and Three-Dimensional Cultures of Transitional Cell Carcinoma Cells¶
  作者：Ann Huygens、Dieter Huyghe、Guy Bormans、Alfons Verbruggen、Appolinary R. Kamuhabwa、Tania Roskams、Peter A. M. de Witte

  DOI：10.1562/0031-8655(2003)078<0607:aapoha>2.0.co;2

  日期：——

  The aim of this study was to investigate the in vitro cellular accumulation, distribution and photocytotoxic effect of hypericin in two-dimensional (2-D) and three-dimensional (3-D) cultured RT-112 transitional cell carcinoma cells of the bladder. In addition, two iodinated derivatives of hypericin were incorporated to investigate whether these analogs, with their increased lipophilicity and heavy-atom effect, display a different biological behavior and optimized photodynamic effect. The results indicate that hypericin and mono-iodohypericin behave similarly in terms of cellular accumulation, spheroidal distribution and photocytotoxic effect. In contrast, di-iodohypericin concentrated to a higher extent in monolayers and spheroids, but the accumulation was restricted to the outermost part of the spheroid. An inverse correlation therefore seems to exist between the extent of cellular uptake under 2-D conditions and the penetration of the compounds in multicellular systems. Moreover, a less pronounced photocytotoxic effect was observed for di-iodohypericin in both 2-D and 3-D cell culture systems. It can be concluded that iodinated derivatives of hypericin do not show an increased cytotoxic effect upon irradiation in either monolayers or spheroids. Moreover, this study shows that when new photosensitizers are preclinically developed, the use of 3-D cell aggregates is critical for a correct evaluation of their efficacy.