2,6-bis(3,4-difluorobenzylidene)cyclohexanone | 892251-79-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: 2,6-bis(3,4-difluorobenzylidene)cyclohexanone
• 英文别名: 2,6-Bis[(3,4-difluorophenyl)methylidene]cyclohexan-1-one
• CAS: 892251-79-5
• 化学式: C₂₀H₁₄F₄O
• mdl: MFCD14722924
• 分子量: 346.324
• InChiKey: ZHPULSQZIKIASZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.46
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  17.07
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为产物：
  描述：

  3,4-二氟苯甲醛 、 环己酮 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 以43%的产率得到2,6-bis(3,4-difluorobenzylidene)cyclohexanone
  参考文献：
  名称：

  In-Vitro and In-Silico Evaluations of Heterocyclic-Containing Diarylpentanoids as Bcl-2 Inhibitors Against LoVo Colorectal Cancer Cells

  摘要：

  在本研究中，我们研究了六种二苯基戊酮类化合物对一系列BRAF和KRAS突变结肠癌细胞系（包括T84、SW620、LoVo、HT29、NCI-H508、RKO和LS411N细胞）的体外抗癌潜力。结构-活性关系研究表明，四氢-4H-噻吩-4-酮和溴苯基团的插入对更好的细胞毒性至关重要。在评估的类似物中，2e被确定为主导化合物，因为它在所有癌细胞系中的低IC50值约为1微米，且具有7.1的高化疗指数。对LoVo细胞的抗增殖研究表明，2e能通过诱导G2/M细胞周期阻滞来抑制细胞增殖和集落形成。随后的细胞凋亡实验证实，2e是一种Bcl-2抑制剂，可以通过直接抑制Bcl-2蛋白而引起内在细胞凋亡，从而产生细胞氧化还原不平衡。进一步的分子对接研究揭示，2e的溴苯基团可以通过疏水相互作用与Bcl-2表面口袋发生相互作用，而四氢-4H-噻吩-4-酮片段可以在同一结合位点形成额外的Pi-硫和Pi-烷基相互作用。总的来说，目前的结果表明，2e可能是一个值得进一步修饰和研究的有效主导化合物，用于开发新的Bcl-2抑制剂。

  DOI：

  10.3390/molecules25173877

文献信息

• Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway
  作者：Pay-Chin Leow、Priti Bahety、Choon Pei Boon、Chong Yew Lee、Kheng Lin Tan、Tianming Yang、Pui-Lai Rachel Ee

  DOI：10.1016/j.ejmech.2013.10.073

  日期：2014.1

  Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/beta-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of beta-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of beta-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than la (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma. (C) 2013 Elsevier Masson SAS. All rights reserved.