5-Chloroindirubin

• 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: 5-Chloroindirubin
• 英文别名: (Z)-5'-chloro-[2,3'-biindolinylidene]-2',3-dione；5'-chloro-1H,1'H-[2,3']biindolylidene-3,2'-dione；(3Z)-5-chloro-3-(3-oxo-1H-indol-2-ylidene)-1H-indol-2-one
• 化学式: C₁₆H₉ClN₂O₂
• 分子量: 296.713
• InChiKey: ANUNRTRKLZJBSN-YPKPFQOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.31
• 重原子数：
  21.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.2
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5-Chloroindirubin 在 吡啶 、 盐酸羟胺 作用下， 以41 %的产率得到(2Z,3E)-5'-chloro-3-(hydroxyimino)-[2,3'-biindolinylidene]-2'-one
  参考文献：
  名称：

  6-Bromoindirubin-3′-oxime derivatives are highly active colistin adjuvants against Klebsiella pneumoniae

  摘要：

  多重耐药（MDR）细菌感染越来越普遍，导致临床医生不得不依赖最后的抗生素，如科利斯汀。

  DOI：

  10.1039/d2md00370h
• 作为产物：
  描述：

  N-(2-羧基)苯基甘氨酸 在 盐酸 、 乙酸酐 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 5.0h， 生成 5-Chloroindirubin
  参考文献：
  名称：

  靛玉红衍生物作为靶向细胞周期蛋白依赖性激酶和组蛋白脱乙酰酶的双重抑制剂用于治疗癌症

  摘要：

  为了利用天然产物靛玉红的独特支架，我们在此采用组合药效团的策略来设计和合成一系列新型靛玉红衍生物，作为针对细胞周期蛋白依赖性激酶 (CDK) 和组蛋白脱乙酰酶 (HDAC) 的双重抑制剂。其中，先导化合物8b具有显着的CDK2/4/6和HDAC6抑制活性，IC 50 = 60.9 ± 2.9、276 ± 22.3、27.2 ± 4.2和128.6 ± 0.4 nM，可有效诱导细胞凋亡和S期在几种癌细胞系中停滞。特别是化合物8b可以通过 Mcl-1/XIAP/PARP 轴阻止非小细胞肺癌细胞系 (A549) 的增殖，这与 HDAC 抑制剂和 CDK 抑制剂联合药物的独特作用模式一致。在 A549 静电复印机模型中，化合物8b显示出与其双重抑制相关的显着抗肿瘤功效。我们的数据表明，化合物8b作为单一药物可能是与 CDK 和 HDAC 抑制剂联合用于癌症治疗的有希望的候选药物。

  DOI：

  10.1021/acs.jmedchem.1c01311

文献信息

• Design, synthesis and biological evaluation of bisindole derivatives as anticancer agents against Tousled-like kinases
  作者：Sung-Bau Lee、Ting-Yu Chang、Nian-Zhe Lee、Zih-Yao Yu、Chi-Yuan Liu、Hsueh-Yun Lee

  DOI：10.1016/j.ejmech.2021.113904

  日期：2022.1

  This study presents the design, synthesis, and characterization of bisindole molecules as anti-cancer agents against Tousled-like kinases (TLKs). We show that compound 2 composed of an indirubin-3′-oxime group linked with a (N-methylpiperidin-2-yl)ethyl moiety possessed inhibitory activity toward both TLK1 and TLK2 in vitro and diminished the phosphorylation level of the downstream substrate anti-silencing

  本研究介绍了双吲哚分子作为抗 Tousled 样激酶 (TLK) 的抗癌剂的设计、合成和表征。我们表明，由与 ( N-甲基哌啶-2-基) 乙基部分连接的靛玉红-3'-肟基团组成的化合物2在体外对 TLK1 和 TLK2 具有抑制活性，并降低下游底物抗磷酸化水平。在复制细胞中沉默功能 1 (ASF1)。化合物2的处理DNA 复制受损，S 期进程减慢，并在复制细胞中引发 DNA 损伤反应。结构优化进一步发现了六种表现出有效的 TLK 抑制活性的衍生物，并揭示了侧链含叔胺部分的重要性。此外，衍生物6、17、19和20强烈抑制三阴性乳腺癌 MDA-MB-231 细胞、非小细胞肺癌 A549 细胞和结肠直肠癌 HCT-116 细胞的生长，而正常肺成纤维细胞MRC5 和 IMR90 细胞对这些化合物的反应较低。总之，本研究将叔胺连接的靛玉红-3'-肟确定为抑制 TLK 活性的有效抗癌剂。
• 6-Bromoindirubin-3′-oxime derivatives are highly active colistin adjuvants against <i>Klebsiella pneumoniae</i>
  作者：Haoting Li、Anne E. Mattingly、Richard D. Smith、Roberta J. Melander、Robert K. Ernst、Christian Melander

  DOI：10.1039/d2md00370h

  日期：——

  Multidrug resistant (MDR) bacterial infections have become increasingly common, leading clinicians to rely on last-resort antibiotics such as colistin.

  多重耐药（MDR）细菌感染越来越普遍，导致临床医生不得不依赖最后的抗生素，如科利斯汀。
• Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells
  作者：Seung Hyun Kim、Si-Wouk Kim、Soo Jeong Choi、Yong-Chul Kim、Tae Sung Kim

  DOI：10.1016/j.bmc.2006.05.044

  日期：2006.10

  The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)(2)D-3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myclocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)(2)D-3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)(2)D-3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25(OH)(2)D-3 or ATRA may improve the ultimate outcomes of APL therapy. (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis and structure–activity relationships of novel indirubin derivatives as potent anti-proliferative agents with CDK2 inhibitory activities
  作者：Myoung Ju Moon、Sang Kook Lee、Jong-Won Lee、Woo Keun Song、Si Wouk Kim、Jae Il Kim、Chunghee Cho、Soo Jeong Choi、Yong-Chul Kim

  DOI：10.1016/j.bmc.2005.08.008

  日期：2006.1

  Indirubin, an active ingredient of a traditional Chinese recipe Danggui Loughui Wan, has been known as it CDK inhibitor competing with ATP for binding to the catalytic site of cyclin-dependent kinases (CDKs). Since CDKs, a group of serine/ threonine kinases forming active heterodimeric complexes with cyclins, are key regulators of the cell cycle regulation, therapeutic interventions targeting CDKs have been stimulated for the treatment of proliferative diseases, such as cancer, psoriasis, and for the prevention of chemotherapy-associated side effects, Such its alopecia. A series of novel indirubin analogs was synthesized and evaluated for anti-proliferative and CDK2 inhibitory activities. Among the indirubin derivatives tested in the growth inhibitions against several human cancer cell lines, 5-nitro, halide, and bulky group Containing acylamino Substituted analogs showed high anti-proliferative effects. Selected analogs showing potent anti-proliferative activities were evaluated further in the CDK2 enzyme assay, Which resulted in the discovery of potent CDK2 inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.
• Indirubin derivatives as bifunctional molecules inducing DNA damage and targeting PARP for the treatment of cancer
  作者：Siyuan Wan、Xinye Chen、Fucheng Yin、Shang Li、Yonglei Zhang、Heng Luo、Zhongwen Luo、Ningjie Cui、Yifan Chen、Xinxin Li、Lingyi Kong、Xiaobing Wang

  DOI：10.1016/j.ejmech.2023.115843

  日期：2023.12