(p-bromobenzyl)-1H-1,2,3-triazol-4-yl-methyl (3β)3-hydroxyolean-12-en-23-(p-bromobenzyl)-1H-1,2,3-triazol-4-yl-methyloxy-28-oate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (p-bromobenzyl)-1H-1,2,3-triazol-4-yl-methyl (3β)3-hydroxyolean-12-en-23-(p-bromobenzyl)-1H-1,2,3-triazol-4-yl-methyloxy-28-oate
• 英文别名: (p-Bromobenzyl)-1H-1,2,3-triazol-4-yl-methyl-(3beta)3-hydroxyolean-12-en-23-(p-bromobenzyl)-1H-1,2,3-triazol-4-ylmethyloxy-28-oate；[1-[(4-bromophenyl)methyl]triazol-4-yl]methyl (4aS,6aR,6aS,6bR,8aR,9R,10S,12aR,14bS)-9-[[1-[(4-bromophenyl)methyl]triazol-4-yl]methoxymethyl]-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylate
• 化学式: C₅₀H₆₄Br₂N₆O₄
• 分子量: 972.904
• InChiKey: XCKCYIXKXKWBMB-UKCHDQOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.3
• 重原子数：
  62
• 可旋转键数：
  12
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  常春藤皂苷元 在 copper(ll) sulfate pentahydrate 、 sodium hydride 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 、 mineral oil 为溶剂， 反应 50.0h， 生成 (p-bromobenzyl)-1H-1,2,3-triazol-4-yl-methyl (3β)3-hydroxyolean-12-en-23-(p-bromobenzyl)-1H-1,2,3-triazol-4-yl-methyloxy-28-oate
  参考文献：
  名称：

  Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives

  摘要：

  Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sotirces, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford as a major product bis-propargylic derivative 1 in 74%. Submitting this compound to Huisgen 1,3 -dipolar cycloaddition reactions with several azides afforded the derivatives 2-19 with yields in the range of 40-87%. All compounds have been screened for in vitro cytotoxic activity in a panel of five human cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the most cytotoxic against all human cancer cell lines with EC50 = 7.4-12.1 mu M. Moreover, leishmanicidal activity was evaluated through the in vitro effect in the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly effective preventing proliferation of intracellular amastigote forms of L infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 mu M, respectively). All these compounds showed a higher selectivity index and low toxicity against two strains of kidney BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in comparison with the commercial antimony drug and is around 8 times more selective than the most active compound previously reported hederagenin derivative. Such high activity associated with low toxicities make the new bis-traiazolyl derivatives promising candidates for the treatment of leishmaniasis. In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51(Li). (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.045

文献信息

• Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives
  作者：Diego Rodríguez-Hernández、Luiz C.A. Barbosa、Antonio J. Demuner、Amalyn Nain-Perez、Sebastião R. Ferreira、Ricardo T. Fujiwara、Raquel M. de Almeida、Lucie Heller、René Csuk

  DOI：10.1016/j.ejmech.2017.09.045

  日期：2017.11

  Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sotirces, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford as a major product bis-propargylic derivative 1 in 74%. Submitting this compound to Huisgen 1,3 -dipolar cycloaddition reactions with several azides afforded the derivatives 2-19 with yields in the range of 40-87%. All compounds have been screened for in vitro cytotoxic activity in a panel of five human cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the most cytotoxic against all human cancer cell lines with EC50 = 7.4-12.1 mu M. Moreover, leishmanicidal activity was evaluated through the in vitro effect in the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly effective preventing proliferation of intracellular amastigote forms of L infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 mu M, respectively). All these compounds showed a higher selectivity index and low toxicity against two strains of kidney BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in comparison with the commercial antimony drug and is around 8 times more selective than the most active compound previously reported hederagenin derivative. Such high activity associated with low toxicities make the new bis-traiazolyl derivatives promising candidates for the treatment of leishmaniasis. In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51(Li). (C) 2017 Elsevier Masson SAS. All rights reserved.