α,α'-bis-veratrylidenecyclopentanone | 106115-49-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: α,α'-bis-veratrylidenecyclopentanone
• 英文别名: 2,5-bis(3,4-dimethoxybenzylidene)cyclopentanone；2,5-diveratrylidene-cyclopentanone；2,5-Diveratryliden-cyclopentanon；Cyclopentanone, 2,5-bis[(3,4-dimethoxyphenyl)methylene]-, (E,E)-；2,5-bis[(3,4-dimethoxyphenyl)methylidene]cyclopentan-1-one
• CAS: 106115-49-5；42019-83-0
• 化学式: C₂₃H₂₄O₅
• mdl: MFCD00121537
• 分子量: 380.441
• InChiKey: NADUQCROZYTGPH-UHFFFAOYSA-N

物化性质

• 熔点：
  188-190 °C
• 沸点：
  585.6±50.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-溴环戊烷羧酸甲酯 、 α,α'-bis-veratrylidenecyclopentanone 在 六甲基磷酰三胺 、 mercury dichloride 、 锌 作用下， 以 乙酸乙酯 、 苯 为溶剂， 反应 4.0h， 以71%的产率得到7'-(3,4-dimethoxybenzylidene)-4'-(3,4-dimethoxyphenyl)-4',5',6',7'-tetrahydro-2'H-spiro[cyclopentane-1,3'-cyclopenta[b]pyran]-2'-one
  参考文献：
  名称：

  Reaction of alicyclic reformatsky reagents with 2,5-bis(arylmethylidene)cyclopentanones

  摘要：

  Reformatsky reaction of methyl 1-bromocyclobutane-, 1-bromocyclopentane-, 1-bromocyclohexane-, and 1-bromocycloheptanecarboxylates with 2,5-bis(arylmethylidene)cyclopentanones gave the corresponding 4'-aryl-7'-arylmethylidene-4',5',6',7'-tetrahydro-2'H-spiro[cycloalkane-1,3-cyclopenta[b]pyran]-2'-ones.

  DOI：

  10.1134/s1070428012060036
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 、 环戊酮 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以44%的产率得到α,α'-bis-veratrylidenecyclopentanone
  参考文献：
  名称：

  Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2013.10.073

文献信息

• Homology Modeling of NAD ⁺ -Dependent DNA Ligase of the Wolbachia Endosymbiont of Brugia malayi and Its Drug Target Potential Using Dispiro-Cycloalkanones
  作者：Nidhi Shrivastava、Jeetendra K. Nag、Jyoti Pandey、Rama Pati Tripathi、Priyanka Shah、Mohammad Imran Siddiqi、Shailja Misra-Bhattacharya

  DOI：10.1128/aac.03449-14

  日期：2015.7

  Lymphatic filarial nematodes maintain a mutualistic relationship with the endosymbiont Wolbachia . Depletion of Wolbachia produces profound defects in nematode development, fertility, and viability and thus has great promise as a novel approach for treating filarial diseases. NAD ⁺ -dependent DNA ligase is an essential enzyme of DNA replication, repair, and recombination. Therefore, in the present study, the antifilarial drug target potential of the NAD ⁺ -dependent DNA ligase of the Wolbachia symbiont of Brugia malayi ( w Bm-LigA) was investigated using dispiro-cycloalkanone compounds. Dispiro-cycloalkanone specifically inhibited the nick-closing and cohesive-end ligation activities of the enzyme without inhibiting human or T4 DNA ligase. The mode of inhibition was competitive with the NAD ⁺ cofactor. Docking studies also revealed the interaction of these compounds with the active site of the target enzyme. The adverse effects of these inhibitors were observed on adult and microfilarial stages of B. malayi in vitro , and the most active compounds were further monitored in vivo in jirds and mastomys rodent models. Compounds 1, 2, and 5 had severe adverse effects in vitro on the motility of both adult worms and microfilariae at low concentrations. Compound 2 was the best inhibitor, with the lowest 50% inhibitory concentration (IC ₅₀ ) (1.02 μM), followed by compound 5 (IC ₅₀ , 2.3 μM) and compound 1 (IC ₅₀ , 2.9 μM). These compounds also exhibited the same adverse effect on adult worms and microfilariae in vivo ( P < 0.05). These compounds also tremendously reduced the wolbachial load, as evident by quantitative real-time PCR ( P < 0.05). w Bm-LigA thus shows great promise as an antifilarial drug target, and dispiro-cycloalkanone compounds show great promise as antifilarial lead candidates.

  摘要 淋巴丝虫与内生共生体 Wolbachia .消耗 沃尔巴克氏体 会造成线虫发育、繁殖力和存活率的严重缺陷，因此有望成为治疗丝虫病的一种新方法。NAD + -依赖性 DNA 连接酶是 DNA 复制、修复和重组过程中必不可少的酶。因此，在本研究中，NAD + 依赖性 DNA 连接酶的抗丝虫药物靶标潜力是研究的重点。 + -依赖性 DNA 连接酶的抗丝虫药物靶点潜力。 沃尔巴克氏体 共生体的 马来布鲁氏菌 ( w Bm-LigA）的二螺环烷酮化合物进行了研究。二螺环烷酮能特异性地抑制该酶的缺口闭合和内聚端连接活性，而对人类或 T4 DNA 连接酶没有抑制作用。其抑制方式与 NAD + 辅助因子的竞争性抑制。对接研究还揭示了这些化合物与目标酶活性位点的相互作用。这些抑制剂对成虫和微丝蚴阶段的 马拉伊蚊 体外 的不利影响，并进一步监测了最具活性的化合物 体内 在鸟类和啮齿动物模型中进行了进一步监测。化合物 1、2 和 5 在体外具有严重的不良影响 在体外 在低浓度下对成虫和微丝蚴的蠕动都有严重的不利影响。化合物 2 是最好的抑制剂，其最低的 50% 抑制浓度（IC 50 ）（1.02 μM），其次是化合物 5（IC 50 为 2.3 μM）和化合物 1（IC 50 为 2.9 μM）。这些化合物对成虫和微丝蚴也表现出同样的不利影响 在体内 ( P 0.05）。通过实时定量 PCR 检测，这些化合物还大大减少了狼尾蚴的数量 ( P 0.05）。 w 因此，Bm-LigA 很有希望成为抗丝虫药物的靶点，二螺环烷酮化合物也很有希望成为抗丝虫的候选先导化合物。
• Stobbe; Haertel, Justus Liebigs Annalen der Chemie, 1909, vol. 370, p. 124
  作者：Stobbe、Haertel

  DOI：——

  日期：——
• Maccioni; Marongiu, Annali di Chimica, 1959, vol. 49, p. 1283,1287
  作者：Maccioni、Marongiu

  DOI：——

  日期：——
• Rao, CH. Bheemasankara; Raju, P. V. Narasimha, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1984, vol. 23, # 4, p. 321 - 327
  作者：Rao, CH. Bheemasankara、Raju, P. V. Narasimha

  DOI：——

  日期：——
• 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.