tetrahydroxytetrahydroberberine hydrochloride

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: tetrahydroxytetrahydroberberine hydrochloride
• 英文别名: Tetrahydroxycanadine HCl；6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline-2,3,9,10-tetrol;hydrochloride
• 化学式: C₁₇H₁₇NO₄*ClH
• 分子量: 335.787
• InChiKey: KTIPNRVQZXOPBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.59
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84.2
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tetrahydroxytetrahydroberberine hydrochloride 在 碘 、 sodium acetate 、 溶剂黄146 、 cesium fluoride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 coptisine iodide
  参考文献：
  名称：

  Cytotoxicity evaluation of natural coptisine and synthesis of coptisine from berberine

  摘要：

  The crude extract (80% MeOH in water) of Chelidonii herba exhibited very interesting cytotoxicity against brine shrimp (Artemia salina Leach) nauplii and cultured human tumour cell in vitro, the colon carcinoma HT 29 (144 h treatment). Fractionation of the crude extract and bioassay-guided procedures showed that the cytotoxic and,the antitumour activities. were concentrated in the basic extract. On the basis of IR, MS and H-1 NMR the compound responsible of the cytotoxic activity was determined to be coptisine. Cytotoxicity evaluation of-coptisine was next extended to-a panel of human and murine cell lines in comparison with the established antitumour drugs mitoxantrone, doxorubicin (D. x) and cisplatin. (CDDP). Coptisine was cytotoxic on LoVo and HT 29 and less potent on L-1210, and it was partially crossresistant on the human tumour colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukaemia cell line resistant to. CD. DP, L-1210/CDDP. Coptisine alkaloid was then synthesised in gram amount from commercial berberine. A four-step synthetic route was elaborated. The overall yield was about 8-10%. The structural identity of synthetic coptisine was verified by IR and NMR methods. A comparison of the cytotoxic effects on the human tumour colon cell line LoVo and on the murine leukaemia L1210 showed, for both natural and synthetic coptisines, a comparable cytotoxic activity more evident against-HT 29 cell line and LoVo. cell line, while the activity was lower against the L1210 cell line. (C) 2001 Editions scientifiques et medicales. Elsevier SAS.

  DOI：

  10.1016/s0014-827x(01)01121-1
• 作为产物：
  描述：

  盐酸小檗碱 在 platinum(IV) oxide 氢气 、 三溴化硼 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、405.3 kPa 条件下， 反应 12.0h， 生成 tetrahydroxytetrahydroberberine hydrochloride
  参考文献：
  名称：

  Cytotoxicity evaluation of natural coptisine and synthesis of coptisine from berberine

  摘要：

  The crude extract (80% MeOH in water) of Chelidonii herba exhibited very interesting cytotoxicity against brine shrimp (Artemia salina Leach) nauplii and cultured human tumour cell in vitro, the colon carcinoma HT 29 (144 h treatment). Fractionation of the crude extract and bioassay-guided procedures showed that the cytotoxic and,the antitumour activities. were concentrated in the basic extract. On the basis of IR, MS and H-1 NMR the compound responsible of the cytotoxic activity was determined to be coptisine. Cytotoxicity evaluation of-coptisine was next extended to-a panel of human and murine cell lines in comparison with the established antitumour drugs mitoxantrone, doxorubicin (D. x) and cisplatin. (CDDP). Coptisine was cytotoxic on LoVo and HT 29 and less potent on L-1210, and it was partially crossresistant on the human tumour colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukaemia cell line resistant to. CD. DP, L-1210/CDDP. Coptisine alkaloid was then synthesised in gram amount from commercial berberine. A four-step synthetic route was elaborated. The overall yield was about 8-10%. The structural identity of synthetic coptisine was verified by IR and NMR methods. A comparison of the cytotoxic effects on the human tumour colon cell line LoVo and on the murine leukaemia L1210 showed, for both natural and synthetic coptisines, a comparable cytotoxic activity more evident against-HT 29 cell line and LoVo. cell line, while the activity was lower against the L1210 cell line. (C) 2001 Editions scientifiques et medicales. Elsevier SAS.

  DOI：

  10.1016/s0014-827x(01)01121-1

文献信息

• Compounds and methods for modulating Rho GTPases
  申请人：Exonhit Therapeutics SA

  公开号：EP2014651A1

  公开（公告）日：2009-01-14

  The present invention relates to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac GTPases (Rac1, Raclb, Rac2 and/or Rac3).

  本发明涉及影响Rho家族GTP酶的GTP结合活性的方法和组合物，优选是Rac GTP酶（Rac1、Raclb、Rac2和/或Rac3）。
• COMPOUNDS AND METHODS FOR MODULATING RHO GTPASES
  申请人：Leblond Bertrand

  公开号：US20100120810A1

  公开（公告）日：2010-05-13

  The present invention relates to methods and compositions that affect the GTP-binding activity of members of the Rho family GTPases, preferably Rac GTPases (Rac1, Rac1b, Rac2 and/or Rac3).

  本发明涉及影响Rho家族GTP酶成员的GTP结合活性的方法和组合物，优选是Rac GTP酶（Rac1，Rac1b，Rac2和/或Rac3）。
• Structure–activity relationship of isoform selective inhibitors of Rac1/1b GTPase nucleotide binding
  作者：Eric Beausoleil、Cédric Chauvignac、Thierry Taverne、Sandrine Lacombe、Laure Pognante、Bertrand Leblond、Diego Pallares、Catherine De Oliveira、Florence Bachelot、Rachel Carton、Hélène Peillon、Séverine Coutadeur、Virginie Picard、Nathalie Lambeng、Laurent Désiré、Fabien Schweighoffer

  DOI：10.1016/j.bmcl.2009.08.037

  日期：2009.10

  The synthesis of a series of berberine, phenantridine and isoquinoline derivatives was realized to explore their Rho GTPase nucleotide inhibitory activity. The compounds were evaluated in a nucleotide binding competition assay against Rac1, Rac1b, Cdc42 and in a cellular Rac GTPase activation assay. The insertion of 19 AA in the splice variant Rac1b is shown to be sufficient to introduce a conformational difference that allows compounds 4, 21, 22, and 26 to exhibit selective inhibition of Rac 1b over Rac1. (C) 2009 Elsevier Ltd. All rights reserved.