5-Benzylidene-2,4-dioxothiazolidine potassium salt | 71995-34-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 5-Benzylidene-2,4-dioxothiazolidine potassium salt
• 英文别名: potassium 5-benzylidene-2,4-dioxothiazolidin-3-ide
• CAS: 71995-34-1
• 化学式: C₁₀H₆NO₂S*K
• 分子量: 243.327
• InChiKey: IEDZLQYSKQLTPO-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.98
• 重原子数：
  15.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.49
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5-Benzylidene-2,4-dioxothiazolidine potassium salt 在 氯乙酸 作用下， 以 甲醇 为溶剂， 反应 0.5h， 生成 5-benzylidene-2,4-thiazolidinedione
  参考文献：
  名称：

  Omar, M. T.; Habashy, M. M.; Kasem, M. A., Journal fur praktische Chemie (Leipzig 1954), 1982, vol. 324, # 3, p. 483 - 487

  摘要：

  DOI：
• 作为产物：
  描述：

  5-benzylidene-2,4-thiazolidinedione 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 以80%的产率得到5-Benzylidene-2,4-dioxothiazolidine potassium salt
  参考文献：
  名称：

  Permuted 2,4-thiazolidinedione (TZD) analogs as GLUT inhibitors and their in-vitro evaluation in leukemic cells

  摘要：

  Cancer is a heterogeneous disease, and its treatment requires the identification of new ways to thwart tumor cells. Amongst such emerging targets are glucose transporters (GLUTs, SLC2 family), which are overexpressed by almost all types of cancer cells; their inhibition provides a strategy to disrupt tumor metabolism selectively, leading to antitumor effects. Here, novel thiazolidinedione (TZD) derivatives were designed, synthesized, characterized, and evaluated for their GLUT1, GLUT4, and GLUT5 inhibitory potential, followed by in-vitro cytotoxicity determination in leukemic cell lines. Compounds G5, G16, and G17 inhibited GLUT1, with IC50, values of 5.4 +/- 1.3, 26.6 +/- 1.8, and 12.6 +/- 1.2 mu M, respectively. G17 was specific for GLUT1, G16 inhibited GLUT4 (IC50 = 21.6 +/- 4.5 mu M) comparably but did not affect GLUT5. The most active compound, G5, inhibited all three GLUT types, with GLUT4 IC50 = 9.5 +/- 2.8 mu M, and GLUT5 IC50 = 34.5 +/- 2.4 mu M. Docking G5, G16, and G17 to the inward- and outward-facing structural models of GLUT1 predicted ligand binding affinities consistent with the kinetic inhibition data and implicated E380 and W388 of GLUT1 vs. their substitutions in GLUT5 (A388 and A396, respectively) in inhibitor preference for GLUT1. G5 inhibited the proliferation of leukemia CEM cells at low micromolar range (IC50 = 13.4 mu M) while being safer for normal blood cells. Investigation of CEM cell cycle progression after treatment with G5 showed that cells accumulated in the G2/M phase. Flow cytometric apoptosis studies revealed that compound G5 induced both early and late-stage apoptosis in CEM cells.

  DOI：

  10.1016/j.ejps.2020.105512

文献信息

• Mechanistic Insights into Binding of Ligands with Thiazolidinedione Warhead to Human Histone Deacetylase 4
  作者：Markus Schweipert、Niklas Jänsch、Neha Upadhyay、Kalpana Tilekar、Ewelina Wozny、Sidra Basheer、Eva Wurster、Marlene Müller、Ramaa C S、Franz-Josef Meyer-Almes

  DOI：10.3390/ph14101032

  日期：——

  kinetics of the molecular recognition of TZD ligands by HDAC4. For this purpose, a structure activity relationship analysis of 225 analogs was combined with a comprehensive study of the enzyme and binding kinetics of a variety of HDAC4 mutant variants. The experimental data were rationalized by docking to the two major conformations of HDAC4. TZD ligands are competitive inhibitors and bind via a two-step

  最近，我们报道了非异羟肟酸噻唑烷二酮 (TZD) 类似物能够抑制人类脱乙酰酶 4 (HDAC4)。本研究旨在剖析 HDAC4 对 TZD 配体分子识别的分子决定因素和动力学。为此，将 225 种类似物的结构活性关系分析与对各种 HDAC4 突变变体的酶和结合动力学的综合研究相结合。通过对接HDAC4的两个主要构象，使实验数据合理化。TZD 配体是竞争性抑制剂，通过涉及主要分子识别和诱导拟合的两步机制结合。24 g 的停留时间为 (34 ± 3) min，因此远大于典型的 pan-HDAC 抑制剂 SAHA ((5 ± 2) min)。重要的，
• Omar, Mohamed T.; Youssef, Ali M., Organic Preparations and Procedures International, 1991, vol. 23, # 3, p. 379 - 382
  作者：Omar, Mohamed T.、Youssef, Ali M.

  DOI：——

  日期：——