N-{6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]hexyl}-1-phenyl-β-carboline-3-carboxamide

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: N-{6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]hexyl}-1-phenyl-β-carboline-3-carboxamide
• 英文别名: N-[6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]hexyl]-1-phenyl-9H-pyrido[3,4-b]indole-3-carboxamide
• 化学式: C₂₇H₂₅Cl₂N₇O
• 分子量: 534.448
• InChiKey: UDMPNTUOKXMTEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-苯基-9H-吡啶并[3,4-b]吲哚-3-羧酸甲酯 在 sodium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 、 乙腈 为溶剂， 反应 37.0h， 生成 N-{6-[(4,6-dichloro-1,3,5-triazin-2-yl)amino]hexyl}-1-phenyl-β-carboline-3-carboxamide
  参考文献：
  名称：

  Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids

  摘要：

  A series of novel hybrids beta-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 mu M. Compounds 9e and 1611) were also active against amastigote forms, displaying IC50 values of 1.0 +/- 0.1 mu M and 1.2 +/- 0.51 mu M, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of beta-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.03.014

文献信息

• Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids
  作者：Paula Baréa、Valéria Aquilino Barbosa、Danielle Lazarin Bidóia、Jéssica Carreira de Paula、Talitha Fernandes Stefanello、Willian Ferreira da Costa、Celso Vataru Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2018.03.014

  日期：2018.4

  A series of novel hybrids beta-carboline-1,3,5-triazine were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and amastigote forms of Leishmania amazonensis. Among the compounds tested, the hybrids 9d, 9e, 16a and 16b showed potent activity against the promastigote forms with IC50 values less than 8 mu M. Compounds 9e and 1611) were also active against amastigote forms, displaying IC50 values of 1.0 +/- 0.1 mu M and 1.2 +/- 0.51 mu M, respectively. Besides that, the hybrid 16b bearing the 4-methoxyphenyl group at C-1 of beta-carboline and isopropylamino group at 1,3,5-triazine, showed low toxicity, being 23.5 and 121.4 times more toxic for promastigotes and axenic amastigotes, respectively, than for macrophage J774-A1 cell lines. Investigation of action mechanism in promastigotes showed that compound 16b caused alterations in cell division cycle and an increase of lipid-storage bodies, leading the cells to death through various factors. The accumulation of lipid bodies may be associated with apoptotic cell death. (C) 2018 Elsevier Masson SAS. All rights reserved.