2-[(4-Fluorophenyl)methylimino]-1,3-thiazolidin-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[(4-Fluorophenyl)methylimino]-1,3-thiazolidin-4-one
• 英文别名: 2-[(4-fluorophenyl)methylimino]-1,3-thiazolidin-4-one
• 化学式: C₁₀H₉FN₂OS
• 分子量: 224.259
• InChiKey: IOGIMHCONDIVLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-吲哚甲醛 、 2-[(4-Fluorophenyl)methylimino]-1,3-thiazolidin-4-one 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以93%的产率得到5-((1H-indol-3-yl)methylene)-2-((4-fluorobenzyl)imino)thiazolidin-4-one
  参考文献：
  名称：

  Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study

  摘要：

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.

  DOI：

  10.1016/j.bioorg.2019.103188
• 作为产物：
  描述：

  对氟苄胺 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 2-[(4-Fluorophenyl)methylimino]-1,3-thiazolidin-4-one
  参考文献：
  名称：

  作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物：设计、合成、生物学评价和分子建模研究

  摘要：

  摘要 在此，我们介绍了作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物的分子设计、化学合成和评价。通过 MTT 测定评估新合成的化合物对 A549（肺癌）、MDA-MB-231 和 BT-471（乳腺癌）、HepG2（肝癌）和 HCT-116（结肠癌）细胞系的体外细胞毒性. 在合成的化合物中，化合物12b对MDA-MB-231细胞系显示出优异的抗癌活性，IC50值为0.95±1.88 μM，并在正常人支气管上皮细胞（Beas-2B）中被证实是安全的。使用形态学观察、AO/EB 和 DAPI 染色程序观察由铅 12b 诱导的细胞凋亡。更多，通过 JC-1 染色还观察到线粒体膜去极化的剂量依赖性增加。膜联蛋白 V-FITC/PI 测定证实 12b 诱导早期细胞凋亡。此外，细胞周期分析表明，MDA-MB-231 细胞在亚 G2/M 期停滞，并抑制微管蛋白聚合，IC50

  DOI：

  10.1016/j.molstruc.2020.128847

文献信息

• New Methods for the Synthesis of 2-Aminothiazolones
  作者：Seb Caille、Eric A. Bercot、Sheng Cui、Margaret M. Faul

  DOI：10.1021/jo702369f

  日期：2008.3.1

  [GRAPHICS]Two new methods for the synthesis of 2-aminothiazolones from 2-(4-methoxybenzylthio)acetic acids are described. A single reagent and simple experimental conditions are used in the key tandem deprotection-cyclization process. In the first approach 2-aminothiazolones are directly accessed via cyclization of the corresponding N-acylisothioureas. The second complementary approach provides access to a variety of 2-thiomethylthiazoiones via cyclization of N-acyldithioimidates. The product 2-thiomethylthiazol ones are then efficiently converted to 2-aminothiazolones via amine displacement.
• Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study
  作者：Dilep Kumar Sigalapalli、Venkatesh Pooladanda、Priti Singh、Manasa Kadagathur、Sravanthi Devi Guggilapu、Jaya Lakshmi Uppu、Neelima D. Tangellamudi、Pavan Kumar Gangireddy、Chandraiah Godugu、Nagendra Babu Bathini

  DOI：10.1016/j.bioorg.2019.103188

  日期：2019.11

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.
• Novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors: Design, synthesis, biological evaluation and molecular modelling studies
  作者：Dilep Kumar Sigalapalli、Venkatesh Pooladanda、Manasa Kadagathur、Sravanthi Devi Guggilapu、Jaya Lakshmi Uppu、Chandraiah Godugu、Nagendra Babu Bathini、Neelima D. Tangellamudi

  DOI：10.1016/j.molstruc.2020.128847

  日期：2021.2

  Abstract Here-in, we present molecular design, chemical synthesis and evaluation of novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors. The newly synthesized compounds were evaluated for their in vitro cytotoxicities against A549 (lung cancer), MDA-MB-231 and BT-471 (breast cancer), HepG2 (liver cancer) and HCT-116 (colon cancer) cell lines by MTT assay

  摘要 在此，我们介绍了作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物的分子设计、化学合成和评价。通过 MTT 测定评估新合成的化合物对 A549（肺癌）、MDA-MB-231 和 BT-471（乳腺癌）、HepG2（肝癌）和 HCT-116（结肠癌）细胞系的体外细胞毒性. 在合成的化合物中，化合物12b对MDA-MB-231细胞系显示出优异的抗癌活性，IC50值为0.95±1.88 μM，并在正常人支气管上皮细胞（Beas-2B）中被证实是安全的。使用形态学观察、AO/EB 和 DAPI 染色程序观察由铅 12b 诱导的细胞凋亡。更多，通过 JC-1 染色还观察到线粒体膜去极化的剂量依赖性增加。膜联蛋白 V-FITC/PI 测定证实 12b 诱导早期细胞凋亡。此外，细胞周期分析表明，MDA-MB-231 细胞在亚 G2/M 期停滞，并抑制微管蛋白聚合，IC50