(Z)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one | 426828-40-2

• 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: (Z)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one
• 英文别名: tetrahydrocurcumin；1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione；(4Z)-5-Hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-4-hepten-3-one
• CAS: 426828-40-2
• 化学式: C₂₁H₂₄O₆
• 分子量: 372.418
• InChiKey: PNTMRHGYQCMNCZ-SSZFMOIBSA-N

物化性质

• 熔点：
  96-97 °C
• 沸点：
  618.6±55.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

四氢姜黄素已知的人体代谢物包括：(2S,3S,4S,5R)-3,4,5-三羟基-6-[4-[3-羟基-7-(4-羟基-3-甲氧基苯基)-5-氧代庚-3-烯基]-2-甲氧基苯氧基]氧杂环己烷-2-羧酸。

Tetrahydrocurcumin has known human metabolites that include (2S,3S,4S,5R)-3,4,5-trihydroxy-6-[4-[3-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-5-oxohept-3-enyl]-2-methoxyphenoxy]oxane-2-carboxylic acid.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  (Z)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one 在 palladium on activated charcoal sodium tetrahydroborate 、 氢气 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 八氢姜黄素
  参考文献：
  名称：

  Metabolism of Curcuminoids in Tissue Slices and Subcellular Fractions from Rat Liver

  摘要：

  Curcumin and its natural congeners are of current interest because of their putative anti-inflammatory and anticarcinogenic activities, but knowledge about their metabolic fate is scant. In the present study conducted with precision-cut liver slices from male and female Sprague-Dawley rats, five reductive but no oxidative metabolites of curcumin and its demethoxy and bis-demethoxy analogues were observed and identified by HPLC and GC-MS analysis, mostly by comparison with authentic reference compounds. The major reductive metabolites were the hexahydrocurcuminoids in both male and female rat liver slices, whereas male rats formed more octahydro than tetrahydro metabolites and female rats more tetrahydro- than octahydrocurcuminoids. Tetrahydro, hexahydro, and octahydro metabolites were predominantly present as glucuronides, but a significant proportion of sulfate conjugates was also observed. The lack of formation of oxidative metabolites of curcumin and the ready generation of reductive metabolites were confirmed using rat liver microsomes and cytosol, respectively. Results of enzymatic hydrolysis studies conducted under various conditions revealed that curcumin and demethoxycurcumin are chemically less stable than bis-demethoxycurcumin, whereas the reductive metabolites of all three curcuminoids are stable compounds. This is the first report on the metabolism of demethoxycurcumin and bis-demethoxycurcumin. In view of the chemical instability of the parent curcuminoids, it is proposed to use their major phase I metabolites, that is, the stable hexahydro products, as biomarkers for exposure in clinical studies.

  DOI：

  10.1021/jf058146a
• 作为产物：
  描述：

  (1E,4Z,6E)-1,7-bis(3-chloro-4-hydroxy-5-methoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 70.0 ℃ 、1.4 MPa 条件下， 以61%的产率得到(Z)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-en-3-one
  参考文献：
  名称：

  卤代姜黄素类似物作为潜在核受体选择性激动剂的合成及生物学评价

  摘要：

  该报告描述了姜黄素类似物的合成及其作为核受体特异性激动剂的分析。姜黄素（CM）是咖喱中的一种姜黄素衍生的生物活性多酚，最近被鉴定为维生素D受体（VDR）的配体，并且CM可能通过直接结合VDR和/或直接发挥其生物作用。核受体超家族中的其他蛋白质。使用哺乳动物二杂交（M2H）和维生素D响应元件（VDRE）生物分析系统，我们测试了CM和11 CM合成类似物激活VDR信号的能力。M2H分析显示CM及其一些类似物诱导RXR和VDR缔合。3人结肠癌细胞（HCT-116）中的（1,25D）配体。在HCT-116中进行了其他实验，利用各种核受体和激素反应性元素确定姜黄素结合的受体特异性。CM似乎没有激活糖皮质激素反应系统中的转录。但是，CM与几个类似物一起引发了视黄酸和类维生素X受体（RXR）响应系统中的转录激活。使用RXR–RXR，VDR–SRC1和VDR–DRIP的M2H分析显示，CM和选择的类似物刺

  DOI：

  10.1016/j.bmc.2012.11.033

文献信息

• Aryl fluorosulfate analogues as potent antimicrobial agents: SAR, cytotoxicity and docking studies
  作者：Lekkala Ravindar、S.N.A. Bukhari、K.P. Rakesh、H.M. Manukumar、H.K. Vivek、N. Mallesha、Zhi-Zhong Xie、Hua-Li Qin

  DOI：10.1016/j.bioorg.2018.08.001

  日期：2018.12

  that the antimicrobial activity depends upon the presence of –OSO2F group and slender effect of different substituent’s on the phenyl rings. The electron donating (OCH3) groups in analogs increase the antibacterial activity, and interestingly the electron withdrawing (Cl, NO2, F and Br) groups increase the antifungal activity (except compound 35, 36 and 37). The mechanism of potent compounds showed membrane

  一系列芳基氟代类似物（的1 - 37）的合成和测试体外抗细菌和抗真菌研究，并通过对接研究验证。化合物9、12、14、19、25、26、35、36和37对测试的细菌菌株显示出优异的抗菌效力，而化合物2、4、5、15、35、36和37被发现具有更好的抗真菌活性分别与标准抗生素庆大霉素和酮康唑相比，可抵抗测试的真菌菌株。在所有的合成37点的类似物，化合物25，26，35，3637和37对金黄色葡萄球菌显示出优异的抗生物膜特性。结构-活性关系（SAR）表明，抗菌活性取决于–OSO 2 F基团的存在以及不同取代基对苯环的细长作用。类似物中的给电子基团（OCH 3）增加了抗菌活性，有趣的是，吸电子基团（Cl，NO 2，F和Br）增加了抗真菌活性（化合物35、36和37除外）。SEM证实了强效化合物的作用机理表明其对细菌的膜损伤。化合物35，36和在分子对接研究中，有37个滑翔g得分最高，并证明了其杀生物性质。
• Different Curcuminoids Inhibit T-Lymphocyte Proliferation Independently of Their Radical Scavenging Activities
  作者：Michael Deters、Heiko Knochenwefel、Daniel Lindhorst、Therese Koal、Hartmut H. Meyer、Wolfram Hänsel、Klaus Resch、Volkhard Kaever

  DOI：10.1007/s11095-008-9579-2

  日期：2008.8

  We investigated the inhibitory effects of curcumin, curcumin derivatives and degradation products on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation and the role of their radical scavenging activity. OKT3-induced human PBMC proliferation was determined by measuring 3H-thymidine incorporation. Radical scavenging activity was evaluated by using an in vitro DPPH assay. OKT3-induced PBMC proliferation was inhibited by curcumin, isocurcumin, bisdesmethoxy-, diacetyl-, tetrahydro-, hexahydro-, and octahydrocurcumin as well as by vanillin, ferulic acid, and dihydroferulic acid with IC50-values of 2.8, 2.8, 6.4, 1.0, 25, 38, 82, 729, 457, and >1,000 μM, respectively. The investigated substances with the strongest effect on radical scavenging were tetrahydro-, hexahydro-, and octahydrocurcumin with IC50 values of 10.0, 11.7, and 12.3 μM, respectively. IC50-values of dihydroferulic acid, ferulic acid, and curcumin were 19.5, 37, and 40 μM. The substances with the lowest radical scavenging activities were vanillin, isocurcumin, diacetylcurcumin, and bisdesmethoxycurcumin with IC50 values higher than 100 μM each. Curcuminoid-induced inhibition of OKT3-induced PBMC proliferation depends on the number of carbon atoms and double bonds of the 1,6-heptadiene-3,5-dione structure as well as on the phenolic ring substitutes of the curcuminoids but is not correlated to their respective radical scavenging activity.

  我们研究了姜黄素、姜黄素衍生物和降解产物对OKT3诱导的人外周血单个核细胞（PBMC）增殖的抑制作用及其自由基清除活性所扮演的角色。通过测定3H-胸苷掺入量来确定OKT3诱导的人PBMC增殖。使用体外DPPH assay评估自由基清除活性。OKT3诱导的PBMC增殖被姜黄素、异姜黄素、双去甲氧基姜黄素、二乙酰姜黄素、四氢姜黄素、六氢姜黄素、八氢姜黄素、香兰素、阿魏酸和二氢阿魏酸以IC50值分别为2.8、2.8、6.4、1.0、25、38、82、729、457和>1000 μM抑制。研究中自由基清除效果最强的物质是四氢姜黄素、六氢姜黄素和八氢姜黄素，IC50值分别为10.0、11.7和12.3 μM。二氢阿魏酸、阿魏酸和姜黄素的IC50值分别为19.5、37和40 μM。自由基清除活性最低的物质是香兰素、异姜黄素、二乙酰姜黄素和双去甲氧基姜黄素，其IC50值均高于100 μM。姜黄素类化合物诱导的OKT3诱导PBMC增殖抑制依赖于1,6-庚二烯-3,5-二酮结构中的碳原子数目和双键，以及姜黄素类化合物的酚环取代基，但与其各自的自由基清除活性无相关性。
• Therapeutic curcumin derivatives
  申请人：Vander Jagt L. David

  公开号：US20070060644A1

  公开（公告）日：2007-03-15

  Curcumin analogues and methods are provided for treatment of disease.

  提供了类姜黄素和治疗疾病的方法。
• THERAPEUTIC CURCUMIN DERIVATIVES
  申请人：STC.UNM

  公开号：US20150011494A1

  公开（公告）日：2015-01-08

  Curcumin analogues and methods are provided for treatment of disease.

  提供了类姜黄素及其方法，用于治疗疾病。
• THERAPEUTIC COMPOSITIONS COMPRISING A COMBINATION OF A HARMINE AND ISOVANILLIN COMPONENT
  申请人：Ions Pharmaceutical S.À R.L.

  公开号：EP3275465A1

  公开（公告）日：2018-01-31

  Human therapeutic treatment compositions comprise the combination of at least one harmine component, and at least one isovanillin component, wherein the components of the composition are different. The compositions are effective for the treatment of human conditions, especially human cancers.

  人类治疗组合物由至少一种禾本科成分和至少一种异香兰素成分组合而成，其中组合物的成分各不相同。这些组合物可有效治疗人类疾病，尤其是人类癌症。