2-methyl-1-(pyrazin-2-ylmethyl)-1H-naphtho[2,3-d]imidazole-4,9-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-methyl-1-(pyrazin-2-ylmethyl)-1H-naphtho[2,3-d]imidazole-4,9-dione
• 英文别名: 2-methyl-3-(pyrazin-2-ylmethyl)benzo[f]benzimidazole-4,9-dione
• 化学式: C₁₇H₁₂N₄O₂
• 分子量: 304.308
• InChiKey: ISCGPQDSEHHKFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  77.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(3-氯-1,4-二氢-1,4-二氧代-2-萘基)乙酰胺 在 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 2.0h， 生成 2-methyl-1-(pyrazin-2-ylmethyl)-1H-naphtho[2,3-d]imidazole-4,9-dione
  参考文献：
  名称：

  Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study

  摘要：

  The anticancer agent YM155 is widely investigated as a specific survivin suppressant. More recently, YM155 was found to induce DNA damage and this has raised doubts as to whether survivin is its primary target. In an effort to assess the contribution of DNA damage to the anticancer activity of YM155, several analogs were prepared and evaluated for antiproliferative activity on malignant cells, participation in DNA intercalation and free radical generation by redox cycling. The intact positively charged scaffold was found to be essential for antiproliferative activity and intercalation but was less critical for redox cycling where the minimal requirement was a pared down bicyclic quinone. Side chain requirements at the N-1 and N-3 positions of the scaffold were more alike for redox cycling and intercalation than antiproliferative activity, underscoring yet again, the limited structural overlaps for these activities. Furthermore, antiproliferative activities were poorly correlated to DNA intercalation and redox cycling. Potent antiproliferative activity (IC50 9-23 nM), exceeding that of YM155, was found for a minimally substituted methyl analog AB7. Like YM155 and other dioxonaphthoimidazoliums, AB7 was a modest DNA intercalator but with weak redox cycling activity. Thus, the capacity of this scaffold to inflict direct DNA damage leading to cell death may not be significant and YM155 should not be routinely classified as a DNA damaging agent. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.026

文献信息

• Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure–activity relationship study
  作者：Si-Han Sherman Ho、Mei-Yi Sim、Wei-Loong Sherman Yee、Tianming Yang、Shyi-Peng John Yuen、Mei-Lin Go

  DOI：10.1016/j.ejmech.2015.09.026

  日期：2015.11

  The anticancer agent YM155 is widely investigated as a specific survivin suppressant. More recently, YM155 was found to induce DNA damage and this has raised doubts as to whether survivin is its primary target. In an effort to assess the contribution of DNA damage to the anticancer activity of YM155, several analogs were prepared and evaluated for antiproliferative activity on malignant cells, participation in DNA intercalation and free radical generation by redox cycling. The intact positively charged scaffold was found to be essential for antiproliferative activity and intercalation but was less critical for redox cycling where the minimal requirement was a pared down bicyclic quinone. Side chain requirements at the N-1 and N-3 positions of the scaffold were more alike for redox cycling and intercalation than antiproliferative activity, underscoring yet again, the limited structural overlaps for these activities. Furthermore, antiproliferative activities were poorly correlated to DNA intercalation and redox cycling. Potent antiproliferative activity (IC50 9-23 nM), exceeding that of YM155, was found for a minimally substituted methyl analog AB7. Like YM155 and other dioxonaphthoimidazoliums, AB7 was a modest DNA intercalator but with weak redox cycling activity. Thus, the capacity of this scaffold to inflict direct DNA damage leading to cell death may not be significant and YM155 should not be routinely classified as a DNA damaging agent. (C) 2015 Elsevier Masson SAS. All rights reserved.