3-methyl-N'-(2-oxoindol-3-yl)-1-benzofuran-2-carbohydrazide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-methyl-N'-(2-oxoindol-3-yl)-1-benzofuran-2-carbohydrazide
• 化学式: C₁₈H₁₃N₃O₃
• 分子量: 319.32
• InChiKey: VHGLZMQCZKXSPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.83
• 重原子数：
  24.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  83.7
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  3-甲基-2-苯并呋喃羧酸乙酯 在 一水合肼 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 4.0h， 生成 3-methyl-N'-(2-oxoindol-3-yl)-1-benzofuran-2-carbohydrazide
  参考文献：
  名称：

  Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer

  摘要：

  DOI：

  10.1080/14756366.2021.1944127

文献信息

• The Anticancer Effects of the Pro-Apoptotic Benzofuran-Isatin Conjugate (5a) Are Associated With p53 Upregulation and Enhancement of Conventional Chemotherapeutic Drug Efficiency in Colorectal Cancer Cell Lines
  作者：Mansoor-Ali Vaali-Mohammed、Maha-Hamadien Abdulla、Sabine Matou-Nasri、Wagdy M. Eldehna、M. Meeramaideen、Eslam B. Elkaeed、Mohammed El-Watidy、Noura S. Alhassan、Khayal Alkhaya、Omar Al Obeed

  DOI：10.3389/fphar.2022.923398

  日期：——

  The present study aimed to investigate in-depth a cytotoxic novel benzofuran-isatin conjugate (5a, 3-methyl-N'-(2-oxoindolin-3-ylidene)benzofuran-2-carbohydrazide) with promising potential anticancer activities in colorectal adenocarcinoma HT29 and metastatic colorectal cancer (CRC) SW620 cell lines. Thus, the primary cell events involved in tumorigenicity, tumor development, metastasis, and chemotherapy response were explored. Both CRC cell lines were exposed to different concentrations of Compound 5a and then subjected to real-time cell viability, migration, and invasion assays, colony formation and cytotoxicity assays, and flow cytometry for cell cycle analysis and apoptosis determination. Western blot and RT-qPCR were performed to assess the protein and transcript expression levels of epithelial-mesenchymal transition (EMT), cell cycle, and apoptosis markers. We showed that the Compound 5a treatment exhibited anticancer effects through inhibition of HT29 and SW620 cell viability, migration, and invasion, in a dose-dependent manner, which were associated with the upregulation of the tumor suppressor p53. Compound 5a also inhibited the colony formation ability of HT29 and SW620 cells and reversed EMT markers E-cadherin and N-cadherin expression. CRC cell exposure to Compound 5a resulted in a cell cycle arrest at the G1/G0 phase in HT29 cells and at the G2/M phase in SW620 cells, along with the downregulation of cyclin A1 expression, described to be involved in the S phase entry. Furthermore, Compound 5a-induced apoptosis was associated with the downregulation of the anti-apoptotic Bcl-xl marker, upregulation of pro-apoptotic Bax and cytochrome c markers, and increased mitochondrial outer membrane permeability, suggesting the involvement of mitochondria-dependent apoptosis pathway. In addition, the combination studies of Compound 5a with the main conventional chemotherapeutic drugs 5-fluorouracil, irinotecan, and oxaliplatin showed a more potent cytotoxic effect in both CRC cells than a single treatment. In conclusion, our findings described the interesting in vitro anticancer properties of Compound 5a, shown to have possible antitumor, antimetastatic, and pro-apoptotic activities, with the enhancement of the cytotoxic efficiency of conventional chemotherapeutic drugs. In vivo studies are requested to confirm the promising anticancer potential of Compound 5a for CRC therapy.

  本研究旨在深入研究一种细胞毒性新型苯并呋喃-异汀共轭物（5a，3-甲基-N'-（2-氧代吲哚啉-3-亚基）苯并呋喃-2-甲酰肼）在结直肠腺癌 HT29 和转移性结直肠癌（CRC）SW620 细胞系中的潜在抗癌活性。因此，我们探讨了参与致瘤性、肿瘤发生、转移和化疗反应的主要细胞事件。将两种 CRC 细胞株暴露于不同浓度的化合物 5a，然后进行实时细胞活力、迁移和侵袭测定、集落形成和细胞毒性测定，以及流式细胞术进行细胞周期分析和细胞凋亡测定。通过 Western 印迹和 RT-qPCR 评估了上皮-间质转化（EMT）、细胞周期和细胞凋亡标志物的蛋白和转录表达水平。结果表明，化合物 5a 通过抑制 HT29 和 SW620 细胞的存活率、迁移和侵袭，以剂量依赖的方式显示出抗癌作用，这与肿瘤抑制因子 p53 的上调有关。化合物 5a 还能抑制 HT29 和 SW620 细胞的集落形成能力，并逆转 EMT 标记 E-cadherin 和 N-cadherin 的表达。CRC 细胞暴露于化合物 5a 会导致 HT29 细胞的细胞周期停滞在 G1/G0 期，SW620 细胞的细胞周期停滞在 G2/M 期，同时细胞周期蛋白 A1 的表达下调，而细胞周期蛋白 A1 被认为参与了 S 期的进入。此外，化合物 5a 诱导的细胞凋亡与抗凋亡 Bcl-xl 标记的下调、促凋亡 Bax 和细胞色素 c 标记的上调以及线粒体外膜通透性的增加有关，表明线粒体依赖性凋亡途径的参与。此外，化合物 5a 与主要的常规化疗药物 5-氟尿嘧啶、伊立替康和奥沙利铂的联合研究表明，与单一治疗相比，化合物 5a 对两种 CRC 细胞都有更强的细胞毒性作用。总之，我们的研究结果描述了化合物 5a 有趣的体外抗癌特性，显示其可能具有抗肿瘤、抗转移和促凋亡活性，并能提高传统化疗药物的细胞毒性效率。需要进行体内研究，以证实化合物 5a 在治疗 CRC 方面的抗癌潜力。
• Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer
  作者：Wagdy M. Eldehna、Rofaida Salem、Zainab M. Elsayed、Tarfah Al-Warhi、Hamada R. Knany、Rezk R. Ayyad、Thamer Bin Traiki、Maha-Hamadien Abdulla、Rehan Ahmad、Hatem A. Abdel-Aziz、Radwan El-Haggar

  DOI：10.1080/14756366.2021.1944127

  日期：2021.1.1