| 1374506-89-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• CAS: 1374506-89-4
• 化学式: C₂₂H₂₂BrNO₇*C₄₂H₇₀O₃₅
• 分子量: 1627.32
• InChiKey: GYKPNBQQLVJDBY-IRRYXVMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -11.59
• 重原子数：
  108.0
• 可旋转键数：
  11.0
• 环数：
  26.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  629.74
• 氢给体数：
  21.0
• 氢受体数：
  43.0

反应信息

• 作为产物：
  描述：

  9-bromonoscapine 、 β-环糊精 以 水 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Molecular Cycloencapsulation Augments Solubility and Improves Therapeutic Index of Brominated Noscapine in Prostate Cancer Cells

  摘要：

  We have previously shown that a novel microtubule-modulating noscapinoid, EM011 (9-Br-Nos), displays potent anticancer activity by inhibition of cellular proliferation and induction of apoptosis in prostate cancer cells and preclinical mice models. However, physicochemical and cellular barriers encumber the development of viable formulations for future clinical translation. To circumvent these limitations, we have synthesized EM011-cyclodextrin inclusion complexes to improve solubility and enhance therapeutic index of EM011. Phase solubility analysis indicated that EM011 formed a 1:1 stoichiometric complex with beta-CD and methyl-beta-CD, with a stability constant (K-c) of 2.42 x 10(-3) M and 4.85 x 10(-3) M, respectively. Fourier transform infrared spectroscopy suggested the penetrance of either a O-CH2 or OCH3-C6H4-OCH3 moiety of EM011 in the beta-CD or methyl-beta-CD cavity. In addition, multifarious techniques, namely, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, NMR spectroscopy, and computational studies validated the cage complex of EM011 with beta-CD and methyl-beta-CD. Moreover, rotating frame overhauser enhancement spectroscopy showed that the H-a proton of the OCH3-C6H4-OCH3 moiety was in close proximity with H3 proton of the beta-CD or methyl-beta-CD cavity. Furthermore, we found that the solubility of EM011 in phosphate buffer saline (pH 7.4) was enhanced by similar to 11 fold and similar to 21 fold upon complexation with beta-CD and methyl-beta-CD, respectively. The enhanced dissolution of the drug CD-complexes in aqueous phase remarkably decreased their IC50 to 28.5 mu M (9-Br-Nos-beta-CD) and 12.5 mu M (9-Br-Nos-methyl-beta-CD) in PC-3 cells compared to free EM011 (similar to 200 mu M). This is the first report to demonstrate the novel construction of cylcodextrin-based nanosupramolecular vehicles for enhanced delivery of EM011 that warrants in vivo evaluation for the superior management of prostate cancer.

  DOI：

  10.1021/mp300063v