3,4,2′,4′-tetramethoxy-trans-stilbene

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3,4,2′,4′-tetramethoxy-trans-stilbene
• 英文别名: 3,4,2',4'-Tetramethoxy-trans-stilbene；1-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-2,4-dimethoxybenzene
• 化学式: C₁₈H₂₀O₄
• 分子量: 300.354
• InChiKey: YFNAWXNNZMEZKQ-FNORWQNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-二甲氧基苄氯 在 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.5h， 生成 3,4,2′,4′-tetramethoxy-trans-stilbene
  参考文献：
  名称：

  3,4,2′-Trimethoxy-trans-stilbene – a potent CYP1B1 inhibitor

  摘要：

  一种新型的含有3,4-二甲氧基基团的反式-苯乙烯系列化合物被设计和合成。评估了3,4-二甲氧基苯乙烯衍生物对细胞色素P450同工酶CYP1A1、CYP1B1和CYP1A2的抑制活性。3,4,2′-三甲氧基反式-苯乙烯（3,4,2′-TMS）对CYP1B1活性表现出极强的抑制作用，IC50为0.004 μM。3,4,2′-TMS在CYP1B1与CYP1A1之间表现出90倍的选择性，在CYP1B1与CYP1A2之间表现出830倍的选择性。然而，3,4,2′,4′-四甲氧基反式-苯乙烯似乎是对CYP1B1和CYP1A1最具选择性的抑制剂，对CYP1A2表现出非常低的亲和力。为了说明苯乙烯衍生物特定的亲和力决定因素，补充实验研究和计算方法被用来解释结构特征如何影响与CYP1A2和CYP1B1结合位点的相互作用。

  DOI：

  10.1039/c3md00317e

文献信息

• Effect of methoxy stilbenes—analogs of resveratrol—on the viability and induction of cell cycle arrest and apoptosis in human myeloid leukemia cells
  作者：Małgorzata Zielińska-Przyjemska、Mariusz Kaczmarek、Violetta Krajka-Kuźniak、Marcin Wierzchowski、Wanda Baer-Dubowska

  DOI：10.1007/s11010-020-03837-0

  日期：2020.11

  The present study aimed to evaluate the cytotoxicity and its mechanism of five synthetic methoxy stilbenes, namely 3,4,4ʹ-trimethoxy, 3,4,2ʹ-trimethoxy, 3,4,2ʹ,4ʹ-tetramethoxy, 3,4,2ʹ,6ʹ-tetramethoxy, and 3,4,2ʹ,4ʹ,6ʹ-pentamethoxy-trans-stilbenes (MS), in comparison with resveratrol (RSV). Human promyelocytic (HL-60) and monocytic leukemia (THP-1) cells were treated with the tested compounds for 24 h, and cytotoxicity, cell cycle distribution, and apoptosis were evaluated. Significant differences were found in the susceptibility of these cell lines to all stilbenes, including RSV. The THP-1 cells were more resistant to cytotoxic activity of these compounds than HL-60 cells. Among the tested stilbenes, 3,4,4ʹ-tri-MS and 3,4,2ʹ,4ʹ-tetra-MS exhibited higher cytotoxicity toward both cell lines than RSV and the other methoxy stilbenes. This activity might be related to cell cycle arrest at the G2/M phase and induction of apoptosis. In this regard, 3,4,4ʹ-tri-MS and 3,4,2ʹ,4ʹ-tetra-MS at highest concentrations increased the p53 protein level particularly in HL-60 cells. Moreover, treatment with these derivatives increased the ratio of the proapoptotic Bax protein to the antiapoptotic Bcl-xl protein, suggesting the induction of apoptosis through the intrinsic mitochondrial pathway in both cell lines. Further studies are required to fully elucidate the mechanism of these activities.

  本研究旨在评估五种合成甲氧基芪脂素（MS）的细胞毒性及其机制，分别为3,4,4ʹ-三甲氧基、3,4,2ʹ-三甲氧基、3,4,2ʹ,4ʹ-四甲氧基、3,4,2ʹ,6ʹ-四甲氧基和3,4,2ʹ,4ʹ,6ʹ-五甲氧基-反式芪脂素，与白藜芦醇（RSV）进行比较。人类早幼粒细胞白血病细胞（HL-60）和单核细胞白血病细胞（THP-1）被处理24小时，评估了细胞毒性、细胞周期分布和凋亡情况。所有芪脂素，包括RSV，对这些细胞系的敏感性存在显著差异。THP-1细胞对这些化合物的细胞毒活性更具抵抗性，而HL-60细胞则更为敏感。在所测试的芪脂素中，3,4,4ʹ-三-MS和3,4,2ʹ,4ʹ-四-MS对两种细胞系的细胞毒性高于RSV和其他甲氧基芪脂素。这种活性可能与在G2/M期阻滞细胞周期和诱导凋亡有关。在这方面，3,4,4ʹ-三-MS和3,4,2ʹ,4ʹ-四-MS在最高浓度下特别增加了HL-60细胞中的p53蛋白水平。此外，使用这些衍生物处理增加了促凋亡Bax蛋白与抗凋亡Bcl-xl蛋白的比值，表明通过内在线粒体途径诱导凋亡在两种细胞系中发生。进一步的研究需要完全阐明这些活性的机制。
• Molho; Coillard, Bulletin de la Societe Chimique de France, 1956, p. 78,90
  作者：Molho、Coillard

  DOI：——

  日期：——
• 3,4,2′-Trimethoxy-trans-stilbene – a potent CYP1B1 inhibitor
  作者：Renata Mikstacka、Marcin Wierzchowski、Zbigniew Dutkiewicz、Agnieszka Gielara-Korzańska、Artur Korzański、Anna Teubert、Stanisław Sobiak、Wanda Baer-Dubowska

  DOI：10.1039/c3md00317e

  日期：——

  A novel series of methoxy-trans-stilbenes with 3,4-dimethoxy motifs was designed and synthesized. The inhibitory potency of 3,4-dimethoxystilbene derivatives against cytochrome P450 isozymes CYP1A1, CYP1B1 and CYP1A2 was evaluated. 3,4,2′-Trimethoxy-trans-stilbene (3,4,2′-TMS) exhibited extremely potent inhibitory action against CYP1B1 activity with an IC50 of 0.004 μM. 3,4,2′-TMS exhibited 90-fold selectivity for CYP1B1 over CYP1A1 and 830-fold selectivity for CYP1B1 over CYP1A2. However, 3,4,2′,4′-tetramethoxy-trans-stilbene appeared to be the most selective inhibitor of both CYP1B1 and CYP1A1 showing very low affinity toward CYP1A2. Complementary experimental studies and computational methods were used to explain what structural determinants decide the specific affinity of stilbene derivatives to CYP1A2 and CYP1B1 binding sites.

  一种新型的含有3,4-二甲氧基基团的反式-苯乙烯系列化合物被设计和合成。评估了3,4-二甲氧基苯乙烯衍生物对细胞色素P450同工酶CYP1A1、CYP1B1和CYP1A2的抑制活性。3,4,2′-三甲氧基反式-苯乙烯（3,4,2′-TMS）对CYP1B1活性表现出极强的抑制作用，IC50为0.004 μM。3,4,2′-TMS在CYP1B1与CYP1A1之间表现出90倍的选择性，在CYP1B1与CYP1A2之间表现出830倍的选择性。然而，3,4,2′,4′-四甲氧基反式-苯乙烯似乎是对CYP1B1和CYP1A1最具选择性的抑制剂，对CYP1A2表现出非常低的亲和力。为了说明苯乙烯衍生物特定的亲和力决定因素，补充实验研究和计算方法被用来解释结构特征如何影响与CYP1A2和CYP1B1结合位点的相互作用。