(3E,5E)-3,5-bis(3-hydroxybenzylidene)-tetrahydropyran-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (3E,5E)-3,5-bis(3-hydroxybenzylidene)-tetrahydropyran-4-one
• 英文别名: (3E,5E)-3,5-bis[(3-hydroxyphenyl)methylidene]oxan-4-one
• 化学式: C₁₉H₁₆O₄
• 分子量: 308.334
• InChiKey: SQIXIHPNIOUPME-BGPOSVGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  四氢吡喃酮 、 间羟基苯甲醛 以 乙醇 为溶剂， 以40.2%的产率得到(3E,5E)-3,5-bis(3-hydroxybenzylidene)-tetrahydropyran-4-one
  参考文献：
  名称：

  New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity

  摘要：

  An overactive Toll-like receptor (TLR) signaling complex is a significant pathogenic factor of acute and chronic inflammatory diseases. The natural product curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid differentiation protein 2), but its low in vivo bioavailability limits its therapeutic potential. We developed new curcumin analogs (MACs) with removal of the beta-diketone moiety and substituted residues in benzene rings, and identify these as potential MD2 inhibitors with improved inhibition potency and stability over that of curcumin. Specifically, MAC 17 and 28 showed the highest anti-inflammatory activity, with >90% inhibition of LPS-stimulated cytokine secretion from macrophages, and protected against LPS-induced acute lung injury and sepsis. The MACs inhibited the TLR4-MD2 signaling complex through competition with LPS for binding on MD2, likely at Arg(90). Our findings indicated that MAC 17 and 28 are promising candidates for future development as therapeutic drugs for inflammatory diseases with an endotoxin etiology. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.02.008

文献信息

• New MD2 inhibitors derived from curcumin with improved anti-inflammatory activity
  作者：Yali Zhang、Zhiguo Liu、Jianzhang Wu、Bin Bai、Hongjin Chen、Zhongxiang Xiao、Lingfeng Chen、Yunjie Zhao、Hazel Lum、Yi Wang、Hong Zhang、Guang Liang

  DOI：10.1016/j.ejmech.2018.02.008

  日期：2018.3

  An overactive Toll-like receptor (TLR) signaling complex is a significant pathogenic factor of acute and chronic inflammatory diseases. The natural product curcumin is reported to inhibit the TLR4 co-receptor, MD2 (myeloid differentiation protein 2), but its low in vivo bioavailability limits its therapeutic potential. We developed new curcumin analogs (MACs) with removal of the beta-diketone moiety and substituted residues in benzene rings, and identify these as potential MD2 inhibitors with improved inhibition potency and stability over that of curcumin. Specifically, MAC 17 and 28 showed the highest anti-inflammatory activity, with >90% inhibition of LPS-stimulated cytokine secretion from macrophages, and protected against LPS-induced acute lung injury and sepsis. The MACs inhibited the TLR4-MD2 signaling complex through competition with LPS for binding on MD2, likely at Arg(90). Our findings indicated that MAC 17 and 28 are promising candidates for future development as therapeutic drugs for inflammatory diseases with an endotoxin etiology. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Synthesis and anti-tumor activity of EF24 analogues as IKKβ inhibitors
  作者：Rong Jin、Qiuxiang Chen、Song Yao、Encheng Bai、Weitao Fu、Ledan Wang、Jiabing Wang、Xiaojing Du、Tao Wei、Haineng Xu、Chengxi Jiang、Peihong Qiu、Jianzhang Wu、Wulan Li、Guang Liang

  DOI：10.1016/j.ejmech.2017.11.077

  日期：2018.1

  EF24 is an IKK beta inhibitor (IC50: 72 mu M) containing various anti-tumor activities. In this study, a series of EF24 analogs targeting IKK beta were designed and synthesized. Several IKK beta inhibitors with better activities than EF24 were screened out and B3 showed best IKK beta inhibitory (IC50: 6.6 mu M). Molecular docking and dynamic simulation experiments further confirmed this inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC-7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF-kappa B signal pathway by inhibiting IKK beta phosphorylation, and followed arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34 expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up-regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and suppressed the IKK beta-NF-kappa B signal pathway in SGC-7901 xenograft model. In total, this study present a potential IKK beta inhibitor as anti-tumor precursor. (C) 2017 Published by Elsevier Masson SAS.