21-p-dimethylaminobenzylidene digoxin

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 21-p-dimethylaminobenzylidene digoxin
• 英文别名: (5Z)-4-[(3S,5R,8R,9S,10S,12R,13S,14S,17R)-3-[(2R,4S,5S,6R)-5-[(2S,4S,5S,6R)-5-[(2S,4S,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-12,14-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-5-[[4-(dimethylamino)phenyl]methylidene]furan-2-one
• 化学式: C₅₀H₇₃NO₁₄
• 分子量: 912.128
• InChiKey: BIAFKPZJIOCNAB-FUFFYMHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  65
• 可旋转键数：
  9
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  206
• 氢给体数：
  6
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  对二甲氨基苯甲醛 、 地高辛 在 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 以63%的产率得到21-p-dimethylaminobenzylidene digoxin
  参考文献：
  名称：

  γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and the Na,K-ATPase activity effect

  摘要：

  Cardiotonic steroids (CS), natural compounds with traditional use in cardiology, have been recently suggested to exert potent anticancer effects. However, the repertoire of molecules with Na, K-ATPase activity and anticancer properties is limited. This paper describes the synthesis of 6 new digoxin derivatives substituted (on the C17-butenolide) with gamma-benzylidene group and their cytotoxic effect on human fibroblast (WI-26 VA4) and cancer (HeLa and RKO) cell lines as well as their effect on Na, K-ATPase activity and expression. As digoxin, compound BD-4 was almost 100-fold more potent than the other derivatives for cytotoxicity with the three types of cells used and was also the only one able to fully inhibit the Na, K-ATPase of HeLa cells after 24 h treatment. No change in the Na, K-ATPase alpha 1 isoform protein expression was detected. On the other hand it was 30-40 fold less potent for direct Na, K-ATPase inhibition, when compared to the most potent derivatives, BD-1 and BD-3, and digoxin. The data presented here demonstrated that the anticancer effect of digoxin derivatives substituted with gamma-benzylidene were not related with their inhibition of Na, K-ATPase activity or alteration of its expression, suggesting that this classical molecular mechanism of CS is not involved in the cytotoxic effect of our derivatives. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.06.028

文献信息

• γ-Benzylidene digoxin derivatives synthesis and molecular modeling: Evaluation of anticancer and the Na,K-ATPase activity effect
  作者：Silmara L.G. Alves、Natasha Paixão、Letícia G.R. Ferreira、Felipe R.S. Santos、Luiza D.R. Neves、Gisele C. Oliveira、Vanessa F. Cortes、Kahlil S. Salomé、Andersson Barison、Fabio V. Santos、Gisele Cenzi、Fernando P. Varotti、Soraya M.F. Oliveira、Alex G. Taranto、Moacyr Comar、Luciana M. Silva、François Noël、Luis Eduardo M. Quintas、Leandro A. Barbosa、José A.F.P. Villar

  DOI：10.1016/j.bmc.2015.06.028

  日期：2015.8

  Cardiotonic steroids (CS), natural compounds with traditional use in cardiology, have been recently suggested to exert potent anticancer effects. However, the repertoire of molecules with Na, K-ATPase activity and anticancer properties is limited. This paper describes the synthesis of 6 new digoxin derivatives substituted (on the C17-butenolide) with gamma-benzylidene group and their cytotoxic effect on human fibroblast (WI-26 VA4) and cancer (HeLa and RKO) cell lines as well as their effect on Na, K-ATPase activity and expression. As digoxin, compound BD-4 was almost 100-fold more potent than the other derivatives for cytotoxicity with the three types of cells used and was also the only one able to fully inhibit the Na, K-ATPase of HeLa cells after 24 h treatment. No change in the Na, K-ATPase alpha 1 isoform protein expression was detected. On the other hand it was 30-40 fold less potent for direct Na, K-ATPase inhibition, when compared to the most potent derivatives, BD-1 and BD-3, and digoxin. The data presented here demonstrated that the anticancer effect of digoxin derivatives substituted with gamma-benzylidene were not related with their inhibition of Na, K-ATPase activity or alteration of its expression, suggesting that this classical molecular mechanism of CS is not involved in the cytotoxic effect of our derivatives. (C) 2015 Elsevier Ltd. All rights reserved.