(11aS)-7-methoxy-8-[4-(2-oxo-1,2-dihydrobenzo[c,d]indol-1-yl)butoxy]-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one | 1357114-08-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (11aS)-7-methoxy-8-[4-(2-oxo-1,2-dihydrobenzo[c,d]indol-1-yl)butoxy]-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one
• 英文别名: (6aS)-2-methoxy-3-[4-(2-oxobenzo[cd]indol-1-yl)butoxy]-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-11-one
• CAS: 1357114-08-9
• 化学式: C₂₈H₂₇N₃O₄
• 分子量: 469.54
• InChiKey: VSRVCLYVJFYAQO-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  71.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-羟基-1,8-萘二甲酰亚胺 在 甲醇 、 tin(II) chloride dihdyrate 、 水 、 sodium hydride 、 对甲苯磺酰氯 、 calcium carbonate 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 (11aS)-7-methoxy-8-[4-(2-oxo-1,2-dihydrobenzo[c,d]indol-1-yl)butoxy]-2,3,5,11a-tetrahydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-5-one
  参考文献：
  名称：

  Design and synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine conjugates as potential anticancer agents

  摘要：

  A series of benzo[c,d]indol-2(1H)one-PBD conjugates (11a-I) have been designed and synthesized as potential anticancer agents. These compounds were prepared by linking the C8-position of DC-81 with a benzo[c,d]indol-2(1H)one moiety through different alkane spacers in good yields and confirmed by H-1 NMR, mass and HRMS data. The DNA binding ability of these conjugates was evaluated by thermal denaturation studies and interestingly, compound 111 showed enhanced DNA binding ability. These compounds were also evaluated for their anticancer activity in selected human cancer cell lines of lung, skin, colon and prostate by using MTT assay method. These new conjugates showed promising anticancer activity with IC50 values ranging from 1.05 to 36.49 mu M. Moreover, cell cycle arrest in SubG1 phase was observed upon treatment of A549 cells with 1 and 2 mu M (IC50) concentrations of compound 111 and it induced apoptosis. This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.003

文献信息

• Design and synthesis of benzo[c,d]indolone-pyrrolobenzodiazepine conjugates as potential anticancer agents
  作者：Ahmed Kamal、G. Ramakrishna、V. Lakshma Nayak、P. Raju、A.V. Subba Rao、A. Viswanath、M.V.P.S. Vishnuvardhan、Sistla Ramakrishna、G. Srinivas

  DOI：10.1016/j.bmc.2011.12.003

  日期：2012.1

  A series of benzo[c,d]indol-2(1H)one-PBD conjugates (11a-I) have been designed and synthesized as potential anticancer agents. These compounds were prepared by linking the C8-position of DC-81 with a benzo[c,d]indol-2(1H)one moiety through different alkane spacers in good yields and confirmed by H-1 NMR, mass and HRMS data. The DNA binding ability of these conjugates was evaluated by thermal denaturation studies and interestingly, compound 111 showed enhanced DNA binding ability. These compounds were also evaluated for their anticancer activity in selected human cancer cell lines of lung, skin, colon and prostate by using MTT assay method. These new conjugates showed promising anticancer activity with IC50 values ranging from 1.05 to 36.49 mu M. Moreover, cell cycle arrest in SubG1 phase was observed upon treatment of A549 cells with 1 and 2 mu M (IC50) concentrations of compound 111 and it induced apoptosis. This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis. (C) 2011 Elsevier Ltd. All rights reserved.