4,5,6-triethylindolin-2-one | 58532-18-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4,5,6-triethylindolin-2-one
• 英文别名: 4,5,6-Trimethoxy-oxindol；4,5,6-trimethoxy-1,3-dihydro-indol-2-one；4,5,6-Trimethoxy-1,3-dihydroindol-2-one；4,5,6-trimethoxy-1,3-dihydroindol-2-one
• CAS: 58532-18-6
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: DNUSKKZUAUUUIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,5,6-triethylindolin-2-one 、 2-氯-1H-吲哚-3-甲醛 在 盐酸 作用下， 以 水 、 溶剂黄146 为溶剂， 以25%的产率得到(3E)-3-[(2-chloro-1H-indol-3-yl)methylidene]-4,5,6-trimethoxy-1H-indol-2-one
  参考文献：
  名称：

  Substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones with antiproliferative activity. Study of the effects on HL-60 leukemia cells

  摘要：

  The synthesis of new substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones is reported. The antiproliferative activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of the most active compound 10 was further investigated in HL-60 leukemia cells. Results obtained show that it causes a block in cell cycle progression, with cell arrest in the G2/M phase, associated with activation of apoptosis accompanied with increased oxidative stress and deregulation of the homeostasis of divalent cations, with significant increase in the cellular concentrations of free Ca2+ and Mg2+. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.004

文献信息

• Synthesis, in vitro and in vivo biological evaluation of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones as new potent anticancer agents
  作者：Rita Morigi、Alessandra Locatelli、Alberto Leoni、Mirella Rambaldi、Roberta Bortolozzi、Elena Mattiuzzo、Roberto Ronca、Federica Maccarinelli、Ernest Hamel、Ruoli Bai、Andrea Brancale、Giampietro Viola

  DOI：10.1016/j.ejmech.2019.01.049

  日期：2019.3

  small library of 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones has been synthesized and screened according to protocols available at the National Cancer Institute (NCI). Some derivatives were potent antiproliferative agents, showing GI50 values in the nanomolar range. Remarkably, when most active compounds against leukemia cells were tested in human peripheral blood lymphocytes from healthy donors

  根据国家癌症研究所（NCI）提供的协议，合成并筛选了3-（5-咪唑并[2,1- b ]噻唑基亚甲基）-2-吲哚满酮的小型文库。一些衍生物是有效的抗增殖剂，在纳摩尔范围内显示GI 50值。值得注意的是，当在健康捐献者的人外周血淋巴细胞中检测到大多数针对白血病细胞的活性化合物时，其细胞毒性要低100-200倍。NCI生物学评估委员会选择了一些化合物，以确定微管蛋白组装抑制作用。此外，对HeLa，HT-29和A549细胞进行的流式细胞术研究表明，化合物14和25在G2 / M阶段造成了封锁。有趣的是，这些衍生物通过线粒体死亡途径诱导细胞凋亡，同时引起caspase-3和-9的显着激活，PARP裂解以及抗凋亡蛋白Bcl-2和Mcl-1的下调。最后，还在小鼠BL6-B16黑色素瘤和E0771乳腺癌细胞中对化合物25进行了体内测试，在两种情况下均导致肿瘤体积显着减少。
• Identification of a new bisindolinone arresting IGROV1 cells proliferation
  作者：Rita Morigi、Chiara Zalambani、Giovanna Farruggia、Laura Verardi、Daniele Esposito、Alberto Leoni、Francesca Borsetti、Manuela Voltattorni、Laura Zambonin、Luca Pincigher、Natalia Calonghi、Alessandra Locatelli

  DOI：10.1016/j.ejmech.2024.116365

  日期：2024.5

  were submitted to the National Cancer Institute for evaluation of antitumor activity in human cell lines. In particular, compound showed remarkable selectivity against IGROV1, an ovarian cancer cell line, without affecting healthy human fibroblast cells. Analyses of cytotoxicity, cell proliferation, cell migration, epigenetic changes, gene expression, and DNA damage were performed to obtain detailed

  在初步筛选中，一系列新型 Knoevenagel 加合物被提交给国家癌症研究所，用于评估人类细胞系的抗肿瘤活性。特别是，该化合物对 IGROV1（一种卵巢癌细胞系）表现出显着的选择性，而不影响健康的人类成纤维细胞。对细胞毒性、细胞增殖、细胞迁移、表观遗传变化、基因表达和 DNA 损伤进行分析，以获得有关其抗肿瘤特性的详细信息。我们的结果表明，它会导致增殖停滞、运动性降低、组蛋白过度乙酰化、细胞周期蛋白 D1 和整合素 β1 基因转录的 α5 亚基下调。此外，治疗会降低细胞周期蛋白 D1 的转录物和蛋白水平，从而增加对电离辐射的敏感性，并导致与细胞周期蛋白 D1 基因沉默相当的 DNA 损伤。
• Antitumor activity and COMPARE analysis of bis-indole derivatives
  作者：Aldo Andreani、Silvia Burnelli、Massimiliano Granaiola、Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Lucilla Varoli、Laura Landi、Cecilia Prata、Francesco Vieceli Dalla Sega、Cristiana Caliceti、Robert H. Shoemaker

  DOI：10.1016/j.bmc.2010.03.063

  日期：2010.5

  This paper reports the synthesis of new derivatives (formed by two indole systems separated by a central moiety) analogous of potent antitumor agents previously described. The activity of the bis-indoles bearing a pyridine core confirms the good result described in the previous paper and compound 4c was chosen for the first in vivo experiment (Hollow Fiber Assay). COMPARE analysis and structure-activity relationships were also considered. Contrary to data reported by other Authors, no correlations were found between antitumor activity and NQO1 induction. (c) 2010 Elsevier Ltd. All rights reserved.
• Substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones with antiproliferative activity. Study of the effects on HL-60 leukemia cells
  作者：Alberto Leoni、Alessandra Locatelli、Rita Morigi、Mirella Rambaldi、Concettina Cappadone、Giovanna Farruggia、Stefano Iotti、Lucia Merolle、Maddalena Zini、Claudio Stefanelli

  DOI：10.1016/j.ejmech.2014.04.004

  日期：2014.5

  The synthesis of new substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones is reported. The antiproliferative activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of the most active compound 10 was further investigated in HL-60 leukemia cells. Results obtained show that it causes a block in cell cycle progression, with cell arrest in the G2/M phase, associated with activation of apoptosis accompanied with increased oxidative stress and deregulation of the homeostasis of divalent cations, with significant increase in the cellular concentrations of free Ca2+ and Mg2+. (C) 2014 Elsevier Masson SAS. All rights reserved.