3'-angeloyloxy-4'-hydroxy-3',4'-dihydroseselin

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3'-angeloyloxy-4'-hydroxy-3',4'-dihydroseselin
• 英文别名: (10-hydroxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-9-yl) (Z)-2-methylbut-2-enoate
• 化学式: C₁₉H₂₀O₆
• 分子量: 344.364
• InChiKey: KJWFOHVSTFGWGZ-YHYXMXQVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  苯乙酸 、 3'-angeloyloxy-4'-hydroxy-3',4'-dihydroseselin 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 、
  参考文献：
  名称：

  3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P-glycoprotein modulators

  摘要：

  摘要：本研究旨在探讨(±)-praeruptorin A (PA)衍生物的多药耐药（MDR）逆转活性。我们发现，所有7,8-吡喃香豆素在调节Pgp方面表现出相等或更高的活性。其中DCK（12）、DMDCK（15）、16、21、23和24在4微米时，可以使抗癌药物长春新碱、阿霉素、普鲁霉素和紫杉醇的IC50值（抑制细胞生长50%的浓度）降低91%∼99%，比其他衍生物更活跃。DMDCK还显著增强了对KB V1异种移植动物模型中紫杉醇的生长抑制作用（P < 0.05），表现出临床应用所需的效力。机制研究表明，这些7,8-吡喃香豆素可能通过直接结合Pgp的底物结合位点或变构位点，从而损害Pgp介导的药物转运，逆转Pgp-MDR。研究结果表明，3′-O、4′-O-芳基酰基取代的7,8-吡喃香豆素可以作为一类新型Pgp调节剂。酰基在维持和增强吡喃香豆素的Pgp调节能力中起着重要作用。3,4-二甲氧基取代的芳基酰基，具有一个可能与Pgp作为氢键受体相互作用的甲氧基，被证明是最有效的逆转MDR。

  DOI：

  10.1111/j.2042-7158.2011.01378.x

文献信息

• Therapeutic agent
  申请人：Enoki Tatsuji

  公开号：US20070092551A1

  公开（公告）日：2007-04-26

  A therapeutic agent and prophylactic agent for a disease accompanying an abnormality in an amount of insulin or insulin response, an agent for an insulin-mimetic action, a food, beverage and feed, an agent for enhancing glucose uptake into a cell, and an agent for inducing differentiation into an adipocyte, characterized in that each comprises as an effective ingredient at least one compound selected from the group consisting of a chalcone compound, an acetophenone compound, a coumarin compound, a phthalide compound, derivatives thereof, and pharmacologically acceptable salts thereof.

  一种治疗伴随胰岛素或胰岛素反应异常的疾病的治疗剂和预防剂，一种具有类胰岛素作用的剂，一种食品、饮料和饲料，一种增强葡萄糖进入细胞的剂，以及一种诱导分化成脂肪细胞的剂，其特征在于每种剂都包含至少一种有效成分，所述有效成分选自香豆素类化合物、苯乙酮类化合物、香豆酮类化合物、邻苯二甲酸酯类化合物及其衍生物和药学上可接受的盐。
• 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins: a new class of P-glycoprotein modulators
  作者：Xiaoling Shen、Guangying Chen、Guoyuan Zhu、Jiazhong Cai、Lu Wang、Yingjie Hu、Wang-Fun Fong

  DOI：10.1111/j.2042-7158.2011.01378.x

  日期：2011.12.8

  P-glycoprotein (Pgp) overexpression in tumour cells leads to multidrug resistance (MDR) and causes failure in cancer chemotherapy. We have previously identified (±)-praeruptorin A (PA) as a potential lead compound for Pgp modulators. In this study we investigated the MDR-reversing activities of PA derivatives.

  Series 7,8-pyranocoumarins with various C-3′ and C-4′ side chains had been semi-synthesized and their MDR-reversing activity was investigated in Pgp-overexpressing MDR tumour cell line HepG2/Dox and in a KB V1 xenograft animal model.

  All 7,8-pyranocoumarins exhibited equal or higher activity in modulating Pgp. DCK (12), DMDCK (15), 16, 21, 23 and 24 at 4 µm achieved 91%∼99% decrease in IC50 value (concentration inhibiting cell growth by 50%) of anticancer agents vinblastine, doxorubicin, puromycin and paclitaxel, and were more active than others. DMDCK also remarkably enhanced the growth inhibitory effect of paclitaxel on KB V1 xenografts (P < 0.05), showing a potency required for clinical usage. Mechanistic studies suggested that these 7,8-pyranocoumarins might reverse Pgp-MDR through directly binding to substrate binding site(s) or allosteric site(s) on Pgp therefore impairing Pgp-mediated drug transport.

  Results from the study suggested that 3′-O, 4′-O-aromatic acyl substituted 7,8-pyranocoumarins could serve as a new class of Pgp modulator. Acyls play an important role in maintaining and enhancing the Pgp-modulating ability of pyranocoumarins. 3,4-Dimethoxyl substituted aromatic acyls, bearing a methoxy that might interact with Pgp as hydrogen bond accepter, were shown to be the most potent for reversing MDR.

  摘要：本研究旨在探讨(±)-praeruptorin A (PA)衍生物的多药耐药（MDR）逆转活性。我们发现，所有7,8-吡喃香豆素在调节Pgp方面表现出相等或更高的活性。其中DCK（12）、DMDCK（15）、16、21、23和24在4微米时，可以使抗癌药物长春新碱、阿霉素、普鲁霉素和紫杉醇的IC50值（抑制细胞生长50%的浓度）降低91%∼99%，比其他衍生物更活跃。DMDCK还显著增强了对KB V1异种移植动物模型中紫杉醇的生长抑制作用（P < 0.05），表现出临床应用所需的效力。机制研究表明，这些7,8-吡喃香豆素可能通过直接结合Pgp的底物结合位点或变构位点，从而损害Pgp介导的药物转运，逆转Pgp-MDR。研究结果表明，3′-O、4′-O-芳基酰基取代的7,8-吡喃香豆素可以作为一类新型Pgp调节剂。酰基在维持和增强吡喃香豆素的Pgp调节能力中起着重要作用。3,4-二甲氧基取代的芳基酰基，具有一个可能与Pgp作为氢键受体相互作用的甲氧基，被证明是最有效的逆转MDR。