1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(1-(2H-chromen-2-oxo-3-yl)ethylidene)hydrazine | 1359132-64-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(1-(2H-chromen-2-oxo-3-yl)ethylidene)hydrazine
• CAS: 1359132-64-1
• 化学式: C₂₀H₁₄ClN₃O₂S
• 分子量: 395.869
• InChiKey: UCRXIAQJJFFOCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  27.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  67.49
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为产物：
  描述：

  3-乙酰基香豆素 在 溶剂黄146 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(1-(2H-chromen-2-oxo-3-yl)ethylidene)hydrazine
  参考文献：
  名称：

  多种噻唑取代香豆素和色酮作为无细胞毒性的ROS和NO抑制剂

  摘要：

  背景：布洛芬，阿司匹林，吲哚美辛，氟芬那酸和苯丁氮酮等非甾体类抗炎药用于治疗大多数炎症。这些非甾体抗炎药还与严重的副作用有关，包括胃溃疡，肾毒性和出血，这主要是由于酸性所致。因此，需要确定针对炎症性疾病的高效且更安全的治疗方法。 方法：本文评估了合成的肼基噻唑取代的香豆素和色酮1-48的ROS抑制活性。从酵母聚糖活化的全血吞噬细胞产生ROS。 结果：在所有测试化合物中，化合物1（IC50 = 38.3±7.1μM），2（IC50 = 5.7±0.2μM），5（IC50 = 28.3±3.5μM），23（IC50 = 12.5±3.1μM），27（与标准布洛芬（IC50 = 54.3±1.9μM）相比，IC50 = 32.8±1.1μM），39（IC50 = 20.2±1.6μM）和42（IC50 = 43.2±3.8μM）表现出强大的ROS抑制作用。而发现化合物3（IC50 = 134.7±1

  DOI：

  10.2174/1570180816666190611155218

文献信息

• Evaluation of a large library of (thiazol-2-yl)hydrazones and analogues as histone acetyltransferase inhibitors: Enzyme and cellular studies
  作者：Simone Carradori、Dante Rotili、Celeste De Monte、Alessia Lenoci、Melissa D'Ascenzio、Veronica Rodriguez、Patrizia Filetici、Marco Miceli、Angela Nebbioso、Lucia Altucci、Daniela Secci、Antonello Mai

  DOI：10.1016/j.ejmech.2014.04.042

  日期：2014.6

  thiazolidines and pyrimidin-4(3H)-ones, and we tested the whole library existing in our lab against human p300 and PCAF HAT enzymes. Some compounds (1x, 1c', 1d', 1i' and 2m) were more efficient than CPTH2 and CPTH6 in inhibiting the p300 HAT enzyme. When tested in human leukemia U937 and colon carcinoma HCT116 cells (100 μM, 30 h), 1x, 1i' and 2m gave higher (U937 cells) or similar (HCT116 cells) apoptosis

  最近，我们描述了一些（噻唑-2-基）azo作为抗原生动物，抗真菌和抗MAO试剂以及Gcn5 HAT抑制剂。在这些最后的化合物中，CPTH2和CPTH6在细胞中显示出HAT抑制作用和广泛的抗癌特性。为了鉴定比两个原型更有效的HAT抑制剂，我们合成了几种新的（噻唑-2-基）azo酮，包括一些相关的噻唑烷和嘧啶4（3 H）-酮，并测试了我们现有的整个文库针对人p300和PCAF HAT酶的实验室。某些化合物（1x，1c '，1d '，1i '和2m）在抑制p300 HAT酶方面比CPTH2和CPTH6更有效。在人白血病U937和结肠癌HCT116细胞（100μM，30小时）中进行测试时，1x，1i '和2m产生的凋亡（U937细胞）或类似细胞（HCT116细胞）高于CPTH6，并且在诱导细胞分化方面比CPTH6更有效（U937细胞）。
• Synthesis of a novel series of thiazole-based histone acetyltransferase inhibitors
  作者：Daniela Secci、Simone Carradori、Bruna Bizzarri、Adriana Bolasco、Paola Ballario、Zoi Patramani、Paola Fragapane、Stefano Vernarecci、Claudia Canzonetta、Patrizia Filetici

  DOI：10.1016/j.bmc.2014.01.022

  日期：2014.3

  Acetylation, which targets a broad range of histone and non-histone proteins, is a reversible mechanism and plays a critical role in eukaryotic genes activation/deactivation. Acetyltransferases are very well conserved through evolution. This allows the use of a simple model organism, such as budding yeast, for the study of their related processes and to discover specific inhibitors. Following a simple yeast-based chemogenetic approach, we have identified a novel HAT (histone acetyltransferase) inhibitor active both in vitro and in vivo. This new synthetic compound,1-(4-(4-chlorophenyl)thiazol-2-yl)-2-(propan-2-ylidene) hydrazine, named BF1, showed substrate selectivity for histone H3 acetylation and inhibitory activity in vitro on recombinant HAT Gcn5 and p300. Finally, we tested BF1 on human cells, HeLa as control and two aggressive cancer cell lines: a neuroblastoma from neuronal tissue and glioblastoma from brain tumour. Both global acetylation of histone H3 and specific acetylation at lysine 18 (H3AcK18) were lowered by BF1 treatment. Collectively, our results show the efficacy of this novel HAT inhibitor and propose the utilization of BF1 as a new, promising tool for future pharmacological studies. (C) 2014 Elsevier Ltd. All rights reserved.