(Z)-4-[(E)-3-(phenylallylidene)-2-(E)-styryl]oxazol-5(4H)-one | 68766-79-0

• 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: (Z)-4-[(E)-3-(phenylallylidene)-2-(E)-styryl]oxazol-5(4H)-one
• 英文别名: (4Z)-2-[(E)-2-phenylethenyl]-4-[(E)-3-phenylprop-2-enylidene]-1,3-oxazol-5-one
• CAS: 68766-79-0
• 化学式: C₂₀H₁₅NO₂
• 分子量: 301.345
• InChiKey: CQLPNSSOUAVJOB-DWVGNRLYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-4-[(E)-3-(phenylallylidene)-2-(E)-styryl]oxazol-5(4H)-one 在 吡啶 、 ammonium acetate 作用下， 反应 18.0h， 以59%的产率得到(Z)-5-[(E)-3-phenylallylidene]-2-(E)-styryl-3,5-dihydro-4H-imidazol-4-one
  参考文献：
  名称：

  Molecular Mimics of Classic P-Glycoprotein Inhibitors as Multidrug Resistance Suppressors and Their Synergistic Effect on Paclitaxel

  摘要：

  P-糖蛋白（Pgp）是一种膜结合的排出泵，分布于各种肿瘤细胞中，被认为是化疗多药耐药性（MDR）的主要成分。在本研究中，合成了三组化合物（咪唑酮、噁唑酮和乙烯基二肽衍生物），旨在开发一种有效抑制MDR的分子框架。在测试它们对Pgp活性的影响时，编号为Cur1-01、Cur1-12V、Curox-1和Curox-3的四种化合物显著降低了剩余ATP浓度，表明Pgp底物结合位点被阻断。另一方面，Cur-3和Cur-10显著增加了剩余ATP浓度，这表明Pgp ATP酶受到抑制。针对表达Pgp/高度耐药的结直肠癌细胞系（LS-174T），检测了合成化合物的细胞毒性。化合物Cur-1和Cur-3显示出明显的细胞毒性，其IC50值分别为7.6和8.9 μM。等毒性组合（在IC50浓度下）的PTX和Cur-3将耐药细胞克隆从45.7%降低到2.5%，尽管其效力从IC50的7.9 nM降至23.8 nM。另一方面，PTX与非细胞毒性的Cur1-12V（10 μM）组合显著降低了PTX的IC50至3.8 nM以及耐药部分至16.2%。利用相同的协议，在另一种耐药的结直肠癌（CRC）细胞系（HCT-116）上确认了组合测试，我们获得了类似的结果。Cur-3和Cur1-12V（10 μM）显著增加了细胞内Pgp探针（多柔比星）的包裹量，使其细胞内浓度从1.9 pmole/cell分别增加到3.0和2.9 pmole/cell。

  DOI：

  10.1371/journal.pone.0168938
• 作为产物：
  描述：

  反式肉桂醛 、 (E)-cinnamoylglycine 在 sodium acetate 、 乙酸酐 作用下， 反应 0.5h， 以83%的产率得到(Z)-4-[(E)-3-(phenylallylidene)-2-(E)-styryl]oxazol-5(4H)-one
  参考文献：
  名称：

  Molecular Mimics of Classic P-Glycoprotein Inhibitors as Multidrug Resistance Suppressors and Their Synergistic Effect on Paclitaxel

  摘要：

  P-糖蛋白（Pgp）是一种膜结合的排出泵，分布于各种肿瘤细胞中，被认为是化疗多药耐药性（MDR）的主要成分。在本研究中，合成了三组化合物（咪唑酮、噁唑酮和乙烯基二肽衍生物），旨在开发一种有效抑制MDR的分子框架。在测试它们对Pgp活性的影响时，编号为Cur1-01、Cur1-12V、Curox-1和Curox-3的四种化合物显著降低了剩余ATP浓度，表明Pgp底物结合位点被阻断。另一方面，Cur-3和Cur-10显著增加了剩余ATP浓度，这表明Pgp ATP酶受到抑制。针对表达Pgp/高度耐药的结直肠癌细胞系（LS-174T），检测了合成化合物的细胞毒性。化合物Cur-1和Cur-3显示出明显的细胞毒性，其IC50值分别为7.6和8.9 μM。等毒性组合（在IC50浓度下）的PTX和Cur-3将耐药细胞克隆从45.7%降低到2.5%，尽管其效力从IC50的7.9 nM降至23.8 nM。另一方面，PTX与非细胞毒性的Cur1-12V（10 μM）组合显著降低了PTX的IC50至3.8 nM以及耐药部分至16.2%。利用相同的协议，在另一种耐药的结直肠癌（CRC）细胞系（HCT-116）上确认了组合测试，我们获得了类似的结果。Cur-3和Cur1-12V（10 μM）显著增加了细胞内Pgp探针（多柔比星）的包裹量，使其细胞内浓度从1.9 pmole/cell分别增加到3.0和2.9 pmole/cell。

  DOI：

  10.1371/journal.pone.0168938

文献信息

• Chemosensitization of resistant Pseudomonas aeruginosa by synthetically related compounds
  申请人：King Abdulaziz University

  公开号：US10842795B1

  公开（公告）日：2020-11-24

  Compounds for the chemosensitization of antibiotic resistant bacteria such as multidrug resistant (MDR) Pseudomonas aeruginosa (Pa) are provided. The compounds inhibit the MDR efflux proteins and re-sensitize the bacteria towards killing by antibiotics. Thus, the compounds are used in combination with antibiotics to treat or prevent infections caused by MDR bacteria.

  本研究提供了用于对抗生素耐药细菌（如多重耐药（MDR）铜绿假单胞菌（Pa））进行化学增敏的化合物。这些化合物可抑制 MDR 外排蛋白，使细菌对抗生素的杀灭作用重新敏感。因此，这些化合物可与抗生素联合使用，治疗或预防由 MDR 细菌引起的感染。
• Introducing of potent cytotoxic novel 2-(aroylamino)cinnamamide derivatives against colon cancer mediated by dual apoptotic signal activation and oxidative stress
  作者：Abdelsattar M. Omar、Moustafa E. El-Araby、Tamer M. Abdelghany、Martin K. Safo、Mostafa H. Ahmed、Rio Boothello、Bhaumik B Patel、Mohamed S. Abdel-Bakky、Azizah M. Malebari、Hany E.A. Ahmed、Radwan S. Elhaggar

  DOI：10.1016/j.bioorg.2020.103953

  日期：2020.8

  Curcumin and trans-cinnamaldehyde are acrolein-based Michael acceptor compounds that are commonly found in domestic condiments, and known to cause cancer cell death via redox mechanisms. Based on the structural features of these compounds we designed and synthesized several 2-cinnamamido-N-substituted-cinnamamide (bis-cinnamamide) compounds. One of the derivatives, (Z)-2-[(E)-cinnamamido]-3-phenyl-N-propylacrylamide 8 showed a moderate antiproliferative potency (HCT-116 cell line inhibition of 32.0 mu M), no inhibition of normal cell lines C-166, and proven cellular activities leading to apoptosis. SAR studies led to more than 10-fold increase in activity. Our most promising compound, [(Z)-3-(1H-indol-3-yl)-N-propyl-2-[(E)-3-(thien-2-yl)propenamido) propenamide] 45 killed colon cancer cells at IC50 = 0.89 mu M (Caco-2), 2.85 mu M (HCT-116) and 1.65 mu M (HT -29), while exhibiting much weaker potency on C-166 and BHK normal cell lines (IC50 = 71 mu M and 77.6 mu M, respectively). Cellular studies towards identifying the compounds mechanism of cytotoxic activities revealed that apoptotic induction occurs in part as a result of oxidative stress. Importantly, the compounds showed inhibition of cancer stem cells that are critical for maintaining the potential for self-renewal and stemness. The results presented here show discovery of covalently acting Michael addition compounds that potently kill cancer cells by a defined mechanism, with prominent selectivity profile over non-cancerous cell lines.
• KASSAB N. A.; HARHASH A. H.; ELBAHAII S. A., Z. NATURFORSCH., 1978, B 33, NO 10, 1145-1149
  作者：KASSAB N. A.、 HARHASH A. H.、 ELBAHAII S. A.

  DOI：——

  日期：——
• Molecular Mimics of Classic P-Glycoprotein Inhibitors as Multidrug Resistance Suppressors and Their Synergistic Effect on Paclitaxel
  作者：Moustafa E. El-Araby、Abdelsattar M. Omar、Maan T. Khayat、Hanan A. Assiri、Ahmed M. Al-Abd

  DOI：10.1371/journal.pone.0168938

  日期：——

  P-glycoprotein (Pgp) is a membrane bound efflux pump spread in a variety of tumor cells and considered as a main component of multidrug resistance (MDR) to chemotherapies. In this work, three groups of compounds (imidazolone, oxazolone and vinyl dipeptide derivatives) were synthesized aiming to develop a molecular framework that effectively suppresses MDR. When tested for their influence on Pgp activity, four compounds coded Cur1-01, Cur1-12V, Curox-1 and Curox-3 significantly decreased remaining ATP concentration indicating Pgp substrate site blocking. On the other hand, Cur-3 and Cur-10 significantly increased remaining ATP concentration, which is indicative of Pgp ATPase inhibition. The cytotoxicity of synthesized compounds was examined against Pgp expressing/highly resistant colorectal cancer cell lines (LS-174T). Compounds Cur-1 and Cur-3 showed considerable cytotoxicity with IC50 values of 7.6 and 8.9 μM, respectively. Equitoxic combination (at IC50 concentrations) of PTX and Cur-3 greatly diminished resistant cell clone from 45.7% to 2.5%, albeit with some drop in potency from IC50 of 7.9 nM to IC50 of 23.8 nM. On the other hand, combination of PTX and the non-cytotoxic Cur1-12V (10 μM) significantly decreased the IC50 of PTX to 3.8 nM as well as the resistant fraction to 16.2%. The combination test was confirmed using the same protocol but on another resistant CRC cell line (HCT-116) as we obtained similar results. Both Cur-3 and Cur1-12V (10 μM) significantly increased the cellular entrapment of Pgp probe (doxorubicin) elevating its intracellular concentration from 1.9 pmole/cell to 3.0 and 2.9 pmole/cell, respectively.

  P-糖蛋白（Pgp）是一种膜结合的排出泵，分布于各种肿瘤细胞中，被认为是化疗多药耐药性（MDR）的主要成分。在本研究中，合成了三组化合物（咪唑酮、噁唑酮和乙烯基二肽衍生物），旨在开发一种有效抑制MDR的分子框架。在测试它们对Pgp活性的影响时，编号为Cur1-01、Cur1-12V、Curox-1和Curox-3的四种化合物显著降低了剩余ATP浓度，表明Pgp底物结合位点被阻断。另一方面，Cur-3和Cur-10显著增加了剩余ATP浓度，这表明Pgp ATP酶受到抑制。针对表达Pgp/高度耐药的结直肠癌细胞系（LS-174T），检测了合成化合物的细胞毒性。化合物Cur-1和Cur-3显示出明显的细胞毒性，其IC50值分别为7.6和8.9 μM。等毒性组合（在IC50浓度下）的PTX和Cur-3将耐药细胞克隆从45.7%降低到2.5%，尽管其效力从IC50的7.9 nM降至23.8 nM。另一方面，PTX与非细胞毒性的Cur1-12V（10 μM）组合显著降低了PTX的IC50至3.8 nM以及耐药部分至16.2%。利用相同的协议，在另一种耐药的结直肠癌（CRC）细胞系（HCT-116）上确认了组合测试，我们获得了类似的结果。Cur-3和Cur1-12V（10 μM）显著增加了细胞内Pgp探针（多柔比星）的包裹量，使其细胞内浓度从1.9 pmole/cell分别增加到3.0和2.9 pmole/cell。