4β-(N'-benzoyl-thioureido)-4-deoxypodophyllotoxin | 1192131-77-3

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: 4β-(N'-benzoyl-thioureido)-4-deoxypodophyllotoxin
• 英文别名: 4β-(benzoylthioureido)-4-deoxypodophyllotoxin；N-[[(5S,5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]carbamothioyl]benzamide
• CAS: 1192131-77-3
• 化学式: C₃₀H₂₈N₂O₈S
• 分子量: 576.627
• InChiKey: LOKKUPBGTSDPRG-QNMIOERPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  41
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  鬼臼毒素 在 迭氮酸 、 palladium on activated charcoal 、 三氟化硼乙醚 、 氢气 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 2.0h， 生成 4β-(N'-benzoyl-thioureido)-4-deoxypodophyllotoxin
  参考文献：
  名称：

  Synthesis and antitumor activity of novel aroylthiourea derivatives of podophyllotoxin

  摘要：

  研究人员合成了一系列新型的4β-[(4-取代)芳基硫脲]荚叶肿毒素衍生物，并通过MTT试验研究了它们抑制癌细胞生长的能力。化合物 4a 对 HepG2、A549 和 HCT-116 癌细胞株具有最高的细胞毒性，IC50 值为 0.1 μM。化合物 4a 诱导的 HCT-116 细胞凋亡可通过 Hoechst33342-碘化丙啶（PI）和吖啶橙（AO）-溴化乙锭（EB）双重染色法进行观察。DNA 流式细胞分析表明，4a 能诱导细胞周期停滞在 G2/M 期，而 kDNA decatenation 分析表明，4a 能抑制拓扑异构酶 IIα 介导的 kDNA decatenation。我们的研究结果表明，化合物 4a 具有良好的抗肿瘤活性，有待进一步研究。

  DOI：

  10.1007/s10637-010-9508-1

文献信息

• Design, synthesis and potent cytotoxic activity of novel podophyllotoxin derivatives
  作者：Wen-Qun Li、Xu-Li Wang、Keduo Qian、Ying-Qian Liu、Chih-Ya Wang、Liu Yang、Jin Tian、Susan L. Morris-Natschke、Xing-Wen Zhou、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2013.01.069

  日期：2013.4

  Twenty new acyl thiourea derivatives of podophyllotoxin and 4'-demethylepipodophyllotoxin were prepared and screened for their cytotoxicity against four human tumor cell lines, A-549, DU-145, KB, and KBvin. With IC50 values of 0.098-1.13 mu M, compounds 13b, 13c, and 13o displayed much better cytotoxic activity than the control etoposide. Most importantly, 13b and 13o exhibited promising cytotoxicity against the drug resistant tumor cell line KBvin with IC50 values of 0.098 and 0.13 mu M, respectively, while etoposide lost activity completely. Structure-activity relationship (SAR) correlations of the new derivatives have been established. Compounds 13b and 13o merit further development as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidates. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and antitumor activity of novel aroylthiourea derivatives of podophyllotoxin
  作者：Yu Zhao、Chengniu Wang、Zhonghua Wu、Jinghuai Fang、Li Zhu

  DOI：10.1007/s10637-010-9508-1

  日期：2012.2

  A novel series of 4β-[(4-substituted) aroylthiourea] derivatives of podophyllotoxin were synthesized and their abilities to inhibit the growth of cancer cells were investigated by MTT assay. Compound 4a possessed the highest cytotoxicity on HepG2, A549 and HCT-116 cancer cell lines with the IC50 values of 0.1 μM. Apoptosis in HCT-116 cells induced by compound 4a was observed by Hoechst33342-Propidium iodide (PI) and acridine orange (AO)-ethidium bromide (EB) double staining assays. DNA flow cytometric analysis revealed that 4a induced cell cycle arrest at G2/M phase and kDNA decatenation assay indicated that 4a inhibited topoisomerase IIα-mediated kDNA decatenation. Our results indicated that compound 4a possessed promising antitumor activity, which need to be studied further.

  研究人员合成了一系列新型的4β-[(4-取代)芳基硫脲]荚叶肿毒素衍生物，并通过MTT试验研究了它们抑制癌细胞生长的能力。化合物 4a 对 HepG2、A549 和 HCT-116 癌细胞株具有最高的细胞毒性，IC50 值为 0.1 μM。化合物 4a 诱导的 HCT-116 细胞凋亡可通过 Hoechst33342-碘化丙啶（PI）和吖啶橙（AO）-溴化乙锭（EB）双重染色法进行观察。DNA 流式细胞分析表明，4a 能诱导细胞周期停滞在 G2/M 期，而 kDNA decatenation 分析表明，4a 能抑制拓扑异构酶 IIα 介导的 kDNA decatenation。我们的研究结果表明，化合物 4a 具有良好的抗肿瘤活性，有待进一步研究。