1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one
• 英文别名: 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one；1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one；MS13
• 化学式: C₁₉H₁₈O₅
• 分子量: 326.349
• InChiKey: ISIMGBQRFXXNON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2-二甲基吲哚 、 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one 在 邻四氯苯醌 、 C₂₄H₃₉OPRu⁽¹⁺⁾*BF₄^(1-) 、 异丙醇 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 36.0h， 以58%的产率得到
  参考文献：
  名称：

  通过与吲哚的螯合辅助偶联反应来催化饱和和不饱和羰基化合物的碳-碳键催化活化

  摘要：

  设计了螯合辅助策略，以促进饱和和不饱和羰基化合物的高度区域选择性催化C–C键活化反应。阳离子的Ru-H络合物1被认为是介导的1,2-二取代的具有α，β不饱和醛和酮的吲哚偶联反应，其中区域选择性C中的，有效的催化剂α -C β活化的羰基片在形成3-烷基吲哚产物中已经实现。用饱和醛和酮的吲哚的类似偶联反应直接导致在C α -C β羰基底物的裂解在形成3-alkylindole产品。1,2-二甲基吲哚与（E的偶联反应）-3-壬烯-2-酮和2-丙醇- d 8显示氘掺入的20-22％至两个α-和β-CH 2 3-alkylindole产物。1,2- dimethylinole与（的偶联反应ë）-3-壬烯-2-酮表现出对产品的α -碳（C最显著碳动力学同位素效应α = 1.046）。由1，2-二甲基吲哚与一系列对位取代的烯酮p -XC 6 H 4 CH = CHCOCH 3（X = OMe，Me，H，Cl，CF

  DOI：

  10.1021/acscatal.0c01245
• 作为产物：
  描述：

  3-甲氧基-4-[(四氢-2H-吡喃-2-基)氧基]苯甲醛 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 7.0h， 生成 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one
  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

• Effects of diarylpentanoid analogues of curcumin on chemiluminescence and chemotactic activities of phagocytes
  作者：Ibrahim Jantan、Syed Nasir Abbas Bukhari、Nordin Haji Lajis、Faridah Abas、Lam Kok Wai、Malina Jasamai

  DOI：10.1111/j.2042-7158.2011.01423.x

  日期：2012.2.6

  A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro.

  The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique.

  Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration.

  The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents.

  摘要 目的 合成了一系列43个姜黄素二芳基戊酮类似物，并评估它们对体外吞噬细胞化学发光和趋化活性的抑制作用。 方法 使用基于流明的化学发光测定法评估化合物对人全血和分离的人多形核白细胞（PMNs）呼吸爆发的影响，并利用Boyden室技术研究它们对PMNs趋化迁移的影响。 主要发现 化合物6、17、25和30在PMNs的氧化爆发上表现出显著的抑制活性。在两个苯环的2和5位置有甲氧基基团，以及在4和2位置分别有甲氧化和氟化基团的存在，可能会显著促进它们对活性氧化物种的抑制活性。化合物7、17、18、24和32显示出对PMNs趋化迁移的强烈抑制作用。在环己酮二芳基戊酮类似物的两个苯环的不同位置进行氯化，导致化合物对PMN迁移具有强效抑制作用。 结论 结果表明，这些二芳基戊酮类似物中的一些能够调节吞噬细胞的先天免疫反应的不同步骤，强调它们作为新的免疫调节剂来源的潜力。
• Antimicrobial Activity of Monoketone Curcuminoids Against Cariogenic Bacteria
  作者：Tatiana M. Vieira、Isabella A. dos Santos、Thayná S. Silva、Carlos H. G. Martins、Antônio E. M. Crotti

  DOI：10.1002/cbdv.201800216

  日期：2018.8

  We evaluated the antimicrobial activity of 25 monoketone curcuminoids (MKCs) against a representative panel of cariogenic bacteria in terms of their minimum inhibitory concentration (MIC) values. Curcumin A (10) displayed promising activity against Streptococcus mutans (MIC = 50 μg/ml) and Streptococcus mitis (MIC = 50 μg/ml) as well as moderate activity against S. sanguinis (MIC = 100 μg/ml), Lactobacillus

  我们根据最低抑菌浓度 (MIC) 值评估了 25 种单酮类姜黄素 (MKC) 对一组有代表性的致龋菌的抗菌活性。姜黄素 A (10) 对变形链球菌 (MIC = 50 μg/ml) 和缓和链球菌 (MIC = 50 μg/ml) 显示出有前景的活性，以及​​对血链球菌 (MIC = 100 μg/ml)、干酪乳杆菌的中等活性(MIC = 100 μg/ml) 和唾液链球菌 (MIC = 200 μg/ml)。结果表明化合物 10 的活性高于其双β-二酮类似物。此外，化合物 3a（1,5-双（4-甲基苯基）戊烷-3-one）和 7b（1,5-双（4-溴苯基）戊烷-3-醇）对 S. mitis 具有中等活性（MIC = 100 μg/ml）和唾液链球菌（MIC = 200 μg/ml）。
• Electrospray ionization tandem mass spectrometry of monoketone curcuminoids
  作者：Tatiana M. Vieira、Renato P. Orenha、Eduardo J. Crevelin、Saulo S.P. Furtado、Ricardo Vessecchi、Renato L.T. Parreira、Antônio E.M. Crotti

  DOI：10.1002/rcm.8699

  日期：2020.9

  reactions of protonated MKCs under collision‐induced dissociation (CID) conditions are still scarce. Here, we combined electrospray ionization tandem mass spectrometry (ESI‐MS/MS) data, multiple‐stage mass spectrometry (MSn), deuterium exchange experiments, accurate‐mass data, and thermochemical data estimated by computational chemistry to elucidate and to rationalize the fragmentation pathways of eleven

  尽管由于其生物活性而对单酮姜黄素（MKC）进行了广泛的研究，但有关碰撞诱导解离（CID）条件下质子化MKC气相裂解反应的数据仍然很少。在这里，我们结合了电喷雾电离串联质谱（ESI-MS / MS）数据，多级质谱（MS n），氘交换实验，精确质量数据和通过计算化学估算的热化学数据，以阐明和合理化11个合成MKC的片段化途径。
• The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells
  作者：Nor Isnida Ismail、Iekhsan Othman、Faridah Abas、Nordin H. Lajis、Rakesh Naidu

  DOI：10.3390/molecules25173798

  日期：——

  The cytotoxic and apoptotic effects of turmeric (Curcuma longa) on colon cancer have been well documented but specific structural modifications of curcumin have been shown to possess greater growth-suppressive potential on colon cancer than curcumin. Therefore, the aim of this study is to identify the anti-cancer properties of curcumin analogue-MS13, a diarylpentanoid on the cytotoxicity, anti-proliferative and apoptotic activity of primary (SW480) and metastatic (SW620) human colon cancer cells. A cell viability assay showed that MS13 has greater cytotoxicity effect on SW480 (EC50: 7.5 ± 2.8 µM) and SW620 (EC50: 5.7 ± 2.4 µM) compared to curcumin (SW480, EC50: 30.6 ± 1.4 µM) and SW620, EC50: 26.8 ± 2.1 µM). Treatment with MS13 at two different doses 1X EC50 and 2X EC50 suppressed the colon cancer cells growth with lower cytotoxicity against normal cells. A greater anti-proliferative effect was also observed in MS13 treated colon cancer cells compared to curcumin at 48 and 72 h. Subsequent analysis on the induction of apoptosis showed that MS13 treated cells exhibited morphological features associated with apoptosis. The findings are also consistent with cellular apoptotic activities shown by increased caspase-3 activity and decreased Bcl-2 protein level in both colon cancer cell lines. In conclusion, MS13 able to suppress colon cancer cell growth by inhibiting cell proliferation and induce apoptosis in primary and metastatic human colon cancer cells.

  姜黄（Curcuma longa）对结肠癌的细胞毒性和凋亡效应已有充分记录，但已显示出姜黄素的特定结构修饰具有比姜黄素更强的对结肠癌生长抑制潜力。因此，本研究旨在确定姜黄素类似物MS13（一种二苯戊二酮）对原发性（SW480）和转移性（SW620）人类结肠癌细胞的细胞毒性、抗增殖和凋亡活性。细胞活力分析表明，与姜黄素相比，MS13对SW480（EC50：7.5 ± 2.8 µM）和SW620（EC50：5.7 ± 2.4 µM）具有更强的细胞毒性效应（SW480，EC50：30.6 ± 1.4 µM和SW620，EC50：26.8 ± 2.1 µM）。用两种不同剂量的MS13处理（1X EC50和2X EC50）抑制了结肠癌细胞的生长，对正常细胞的细胞毒性较低。MS13处理的结肠癌细胞也观察到更强的抗增殖效应，比姜黄素在48和72小时时更显著。随后对凋亡诱导的分析显示，MS13处理的细胞表现出与凋亡相关的形态特征。研究结果还与细胞凋亡活性一致，显示了两种结肠癌细胞系中caspase-3活性增加和Bcl-2蛋白水平降低。总之，MS13能够通过抑制细胞增殖和诱导原发性和转移性人类结肠癌细胞的凋亡来抑制结肠癌细胞的生长。
• Synthesis and biological evaluation of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one and its aminomethyl derivatives
  作者：Kadir Ozden Yerdelen、Halise Inci Gul、Hiroshi Sakagami、Naoki Umemura

  DOI：10.3109/14756366.2014.940934

  日期：2015.5.4

  Aminomethyl derivatives of 1,5-bis(4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one, designed as new cytotoxins, were synthesized and evaluated in terms of their cytotoxic activities. The compounds have low CC50 values in the low micromolar range against HL-60 neoplasms and HSC-2, HSC-3 and HSC-4 carcinoma cells. In general, the average CC50 values of these compounds were higher towards HGF, HPC and

  合成了被设计为新的细胞毒素的1,5-双（4-羟基-3-甲氧基苯基）戊-1,4-二烯-3-酮的氨基甲基衍生物，并对其细胞毒性进行了评估。这些化合物在针对HL-60肿瘤以及HSC-2，HSC-3和HSC-4癌细胞的低微摩尔范围内具有较低的CC50值。通常，这些化合物对HGF，HPC和HPLF非恶性细胞的平均CC50值较高，这揭示了这些氨甲基衍生物曼尼希碱的肿瘤选择性。使用特定浓度的化合物4和6会导致HSC-2细胞而非HGF细胞裂解PARP1，这可能是造成细胞毒性和肿瘤选择性的一个因素。