3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)propenone | 383175-35-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)propenone
• 英文别名: 3-(4-Bromophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 383175-35-7
• 化学式: C₁₈H₁₇BrO₄
• 分子量: 377.235
• InChiKey: RWYIXEHZSKOXEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)propenone 在 双氧水 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以56%的产率得到3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)-2,3-epoxypropanone
  参考文献：
  名称：

  抗癌查尔酮环氧化物抑制细胞周期和诱导细胞凋亡

  摘要：

  用于治疗胰腺癌的安全有效的化学治疗剂仍然难以捉摸。我们发现查尔酮环氧化物（1,3-二芳基-2,3-环氧丙酮）抑制了两种胰腺癌细胞系 BxPC-3 和 MIA PaCa-2 的生长。三种化合物具有活性，GI50 值为 5.6 至 15.8 µM。化合物 4a，1,3-双（3,4,5-三甲氧基苯基）-2,3-环氧丙酮，在 NCI 60-细胞系面板中的平均 GI50 为 14.1 µM。为了研究作用模式，对 BxPC-3 细胞进行了细胞周期分析。用 50 µM 4a 处理细胞导致 G2 / M 的显着积累（4a 12 小时后为 61%，未处理细胞为 15%）。细胞迅速进入凋亡。12 小时后，26% 的用 50 µM 4a 处理的细胞进入细胞凋亡，而用 100 µM 依托泊苷处理的细胞为 4%，未处理的细胞为 2%。化合物 4a 干扰了紫杉醇对微管蛋白聚合的增强，表明微管是作用位点。硫醇亲核试剂在碱性条件下与

  DOI：

  10.1002/ardp.200900261
• 作为产物：
  描述：

  4-溴苯乙酮 、 3,4,5-三甲氧基苯甲醛 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 生成 3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)propenone
  参考文献：
  名称：

  Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines

  摘要：

  A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration. Amongst the synthesized derivatives, compounds HK-2, HK-10 and HK-13 were found to be effective against all the three cancer cell lines. HK-2 exhibited IC50 values of 3.39 mu M, 4.78 mu M and 4.23 mu M, HK-10 showed IC50 values of 0.81 mu M, 5.89 mu M, 4.96 mu M and HK-13 showed IC50 values 3.24 mu M, 4.93 mu M and 4.73 mu M against MDA-MB-231, HCT-116 and HT-29 cancer cell lines, respectively. HK-10 was found to be the most potent compound in the series with IC50 values of 0.81 mu M against MDA-MB-231. In the cell cycle analysis, HK-2 and HK-10 showed cell arrest at G2/M phase of the cell cycle while HK-13 inhibited cell growth at the G1/G0 phase. All the three compounds showed cell death induced through apoptosis. In the docking studies, HK-2, HK-10 and HK-13 were found to fit well in the colchicine binding site of the tubulin. Some of the compounds in the current series were found to be promising against all the three cancer cell lines and may act as potent leads for further development.

  DOI：

  10.1016/j.bmcl.2020.127468

文献信息

• Synthesis of novel pyrazoline derivatives and the evaluation of death mechanisms involved in their antileukemic activity
  作者：Natália Marceli Stefanes、Jéssica Toigo、Mariana Franzoni Maioral、Amanda Virtuoso Jacques、Louise Domeneghini Chiaradia-Delatorre、Daiane Mari Perondi、Amanda Abdalla Biasi Ribeiro、Álisson Bigolin、Iris Mattos Santos Pirath、Bruna Fischer Duarte、Ricardo José Nunes、Maria Cláudia Santos-Silva

  DOI：10.1016/j.bmc.2018.12.012

  日期：2019.1

  therefore, the search for new molecules with antitumor activity, specific and selective for neoplastic cells, became a great challenge for researchers in the oncology field. As pyrazolines stand out in the literature for their great variety of biological activities, the aim of this study was to synthesize and evaluate the antileukemic activity of five new pyrazoline derivatives. All pyrazolines showed

  恶性肿瘤是全球范围内主要的死亡原因之一，血液系统恶性肿瘤包括急性白血病（AL）是最相关的癌症类型之一。当前可用的化学疗法与高发病率和高死亡率相关，因此，寻找对肿瘤细胞具有特异性和选择性的，具有抗肿瘤活性的新分子，成为肿瘤学领域研究人员的巨大挑战。由于吡唑啉因其多种生物活性而在文献中脱颖而出，因此本研究的目的是合成和评估五种新的吡唑啉衍生物的抗白血病活性。所有吡唑啉均具有足够的理化性质，具有良好的口服生物利用度。选择了两种未公开和最有效的吡唑啉衍生物用于进一步的实验。与非肿瘤细胞相比，这些化合物对白血病细胞具有高度选择性，并且不会引起人红细胞的裂解。此外，选定的吡唑啉诱导细胞周期停滞在G0 / G1期，并降低了细胞增殖标志物KI67。通过形态分析，评估磷脂酰丝氨酸残基暴露和DNA片段化，证实了所选吡唑啉诱导的凋亡细胞死亡。几个因素表明发生内在和外在凋亡。它们是：FasR表达增加；Bax在Bc
• Synthesis of New <i>N</i><sup>1</sup>-Substituted-5-aryl-3-(3,4,5-trimethoxyphenyl)-2-pyrazoline Derivatives as Antitumor Agents Targeting the Colchicine Site on Tubulin
  作者：Salwa Elmeligie、Nadia Abdalla Khalil、Eman Mohamed Ahmed、Soha Hussein Emam、Sawsan Abo-Bakr Zaitone

  DOI：10.1248/bpb.b16-00277

  日期：——

  A series of pyrazoline derivatives 2a–e, 3a–e and 4a–e structurally related to combretastatin A4 (CA-4) were synthesized and characterized by spectroscopic means and elemental analyses. In these compounds, the cis double bond of CA-4 was replaced with the pyrazoline ring aiming to enhance the cytotoxic effects displayed by CA-4 and to prevent the cis/trans isomerization that is associated with inactivation of CA-4. The cytotoxic activity of all new compounds was investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by the most active compounds 3d, 4a and e was evaluated. The cytotoxicity of 4e was correlated with induction of apoptosis and caspase-3 activation in vitro thus indicating the apoptotic pathway of anticancer effect of these compounds. Furthermore, in vivo evaluation of the synthesized compounds was carried out against Ehrlich’s ascites carcinoma (EAC) solid tumor grown in mice. Compounds 2c, 3a and e showed significant reduction in tumor weight, and about 2–4 fold increase in caspase-3 expression.

  合成了一系列与康柏拉斯汀A4（CA-4）结构相关的吡唑啉衍生物2a–e、3a–e和4a–e，并通过光谱学方法和元素分析进行了表征。在这些化合物中，CA-4的顺式双键被吡唑啉环取代，旨在增强CA-4表现出的细胞毒性作用，并防止与CA-4失活相关的顺/反异构化。所有新化合物的细胞毒性活性在体外对MCF-7和HCT-116细胞系进行了研究。对最活跃化合物3d、4a和e的微管聚合抑制作用进行了评估。体外研究表明，化合物4e的细胞毒性与凋亡诱导和caspase-3活化相关，因此指示了这些化合物的抗癌效果的凋亡途径。此外，对合成化合物在小鼠中的埃赫利希腹水癌（EAC）实体肿瘤进行了体内评估。化合物2c、3a和e显示出肿瘤重量显著降低，以及caspase-3表达增加约2–4倍。
• Identification of 3′,4′,5′-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells
  作者：Chih-Ho Lai、Yerra Koteswara Rao、Shih-Hua Fang、Yu-Ting Sing、Yew-Min Tzeng

  DOI：10.1016/j.bmcl.2010.07.094

  日期：2010.9

  Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective compounds 1, 7, and 13 also showed the bactericide activity against the reference as well as multidrug-resistant strains of H. pylori. Additionally, the aforementioned three compounds potentially inhibited the H. pylori adhesion and invasion to human gastric epithelial (AGS) cells. Furthermore, these selective compounds inhibited the H. pylori-induced gastric inflammation by reduced inflammatory mediator's nuclear factor kappa B activation, and the secretion of interleukin-8. (c) 2010 Elsevier Ltd. All rights reserved.
• Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines
  作者：Ashish Ranjan Dwivedi、Vijay Kumar、Harmeet Kaur、Naveen Kumar、Ravi Prakash Yadav、Ramarao Poduri、Somesh Baranwal、Vinod Kumar

  DOI：10.1016/j.bmcl.2020.127468

  日期：2020.10

  A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration. Amongst the synthesized derivatives, compounds HK-2, HK-10 and HK-13 were found to be effective against all the three cancer cell lines. HK-2 exhibited IC50 values of 3.39 mu M, 4.78 mu M and 4.23 mu M, HK-10 showed IC50 values of 0.81 mu M, 5.89 mu M, 4.96 mu M and HK-13 showed IC50 values 3.24 mu M, 4.93 mu M and 4.73 mu M against MDA-MB-231, HCT-116 and HT-29 cancer cell lines, respectively. HK-10 was found to be the most potent compound in the series with IC50 values of 0.81 mu M against MDA-MB-231. In the cell cycle analysis, HK-2 and HK-10 showed cell arrest at G2/M phase of the cell cycle while HK-13 inhibited cell growth at the G1/G0 phase. All the three compounds showed cell death induced through apoptosis. In the docking studies, HK-2, HK-10 and HK-13 were found to fit well in the colchicine binding site of the tubulin. Some of the compounds in the current series were found to be promising against all the three cancer cell lines and may act as potent leads for further development.
• Cell Cycle Arrest and Apoptosis Induction by an Anticancer Chalcone Epoxide
  作者：Haiyong Han、Yu Zhao、Timothy Cuthbertson、Rosemarie F. Hartman、Seth D. Rose

  DOI：10.1002/ardp.200900261

  日期：——

  were carried out. Treatment of cells with 50 µM 4a resulted in dramatic accumulation at G2/M (61% after 12 h for 4a vs. 15% for untreated cells). The cells rapidly entered apoptosis. After 12 h, 26% of cells treated with 50 µM 4a had entered apoptosis vs. 4% for cells treated with 100 µM etoposide and 2% for untreated cells. Compound 4a interfered with paclitaxel enhancement of tubulin polymerization,

  用于治疗胰腺癌的安全有效的化学治疗剂仍然难以捉摸。我们发现查尔酮环氧化物（1,3-二芳基-2,3-环氧丙酮）抑制了两种胰腺癌细胞系 BxPC-3 和 MIA PaCa-2 的生长。三种化合物具有活性，GI50 值为 5.6 至 15.8 µM。化合物 4a，1,3-双（3,4,5-三甲氧基苯基）-2,3-环氧丙酮，在 NCI 60-细胞系面板中的平均 GI50 为 14.1 µM。为了研究作用模式，对 BxPC-3 细胞进行了细胞周期分析。用 50 µM 4a 处理细胞导致 G2 / M 的显着积累（4a 12 小时后为 61%，未处理细胞为 15%）。细胞迅速进入凋亡。12 小时后，26% 的用 50 µM 4a 处理的细胞进入细胞凋亡，而用 100 µM 依托泊苷处理的细胞为 4%，未处理的细胞为 2%。化合物 4a 干扰了紫杉醇对微管蛋白聚合的增强，表明微管是作用位点。硫醇亲核试剂在碱性条件下与