3-hydroxy-3',4',5'-trimethoxychalcone | 903676-81-3

• 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-hydroxy-3',4',5'-trimethoxychalcone
• 英文别名: 3-(3-Hydroxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one；3-(3-hydroxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 903676-81-3
• 化学式: C₁₈H₁₈O₅
• 分子量: 314.338
• InChiKey: OIDIAFSYSYRBHZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 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：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苄脒盐酸盐 、 3-hydroxy-3',4',5'-trimethoxychalcone 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 11.0h， 以50%的产率得到3-(2-phenyl-6-(3,4,5-trimethoxyphenyl)pyrimidin-4-yl)phenol
  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
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 、 间羟基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 0.08h， 生成 3-hydroxy-3',4',5'-trimethoxychalcone
  参考文献：
  名称：

  Structure−Activity Relationship Studies of Chalcone Leading to 3-Hydroxy-4,3′,4′,5′-tetramethoxychalcone and Its Analogues as Potent Nuclear Factor κB Inhibitors and Their Anticancer Activities

  摘要：

  Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappa B) activation. The structures of chalcone-based NF-kappa B inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappa B inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappa B inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappa B inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappa B inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappa B inhibitory activities, suggesting that suppressing NF-kappa B activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.

  DOI：

  10.1021/jm901278z

文献信息

• Structure−Activity Relationship Studies of Chalcone Leading to 3-Hydroxy-4,3′,4′,5′-tetramethoxychalcone and Its Analogues as Potent Nuclear Factor κB Inhibitors and Their Anticancer Activities
  作者：Balasubramanian Srinivasan、Thomas E. Johnson、Rahul Lad、Chengguo Xing

  DOI：10.1021/jm901278z

  日期：2009.11.26

  Chalcone is a privileged structure, demonstrating promising anti-inflammatory and anticancer activities. One potential mechanism is to suppress nuclear factor kappa B (NF-kappa B) activation. The structures of chalcone-based NF-kappa B inhibitors vary significantly that there is minimum information about their structure-activity relationships (SAR). This study aims to establish SAR of chalcone-based compounds to NF-kappa B inhibition, to explore the feasibility of developing simple chalcone-based potent NF-kappa B inhibitors, and to evaluate their anticancer activities. Three series of chalcones were synthesized in one to three steps with the key step being aldol condensation. These candidates demonstrated a wide range of NF-kappa B inhibitory activities, some of low micromolar potency, establishing that structural complexity is not required for NF-kappa B inhibition. Lead compounds also demonstrate potent cytotoxicity against lung cancer cells. Their cytotoxicities correlate moderately well with their NF-kappa B inhibitory activities, suggesting that suppressing NF-kappa B activation is likely responsible for at least some of the cytotoxicities. One lead compound effectively inhibits lung tumor growth with no signs of adverse side effects.
• Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives
  作者：Cenzo Congiu、Valentina Onnis、Loredana Vesci、Massimo Castorina、Claudio Pisano

  DOI：10.1016/j.bmc.2010.07.037

  日期：2010.9

  A series of 3,5-diaryl-4,5-dihydropyrazole regioisomers, and their 1-acetylated derivatives, bearing a 3,4,5-trimethoxyphenyl moiety combined with a variety of substituted phenyl rings, was synthesized and evaluated for antitumor activity. Results of the in vitro assay against a non-small cell lung carcinoma cell line (NCI-H460) showed several compounds to be endowed with cytotoxicity in micromolar to sub-micromolar range, depending on substitution pattern and position of aryl rings on 4,5-dihydropyrazole core. Potent and selective activity was also observed in the NCI 60 human cancer cell line panel. 5-(3,4,5-Trimethoxyphenyl) pyrazolines 31 and 39 were found to possess potent antiproliferative activity against SR and MDA-MB-435, with GI(50) inhibitory values in nanomolar range. Structure-activity relationships revealed that introduction of a (hydroxy) acetyl group at N-1 of inactive 5-(3,4,5-trimethoxyphenyl) pyrazolines, results in a clear in vitro activating effect. Compound 31 (IC(50) = 5.16 mu M) showed inhibition of tubulin polymerization comparable to that of CA-4 (IC(50) = 4.92 mu M). (C) 2010 Elsevier Ltd. All rights reserved.
• Examination of growth inhibitory properties of synthetic chalcones for which antibacterial activity was predicted
  作者：Daniela Batovska、Stoyan Parushev、Bistra Stamboliyska、Iva Tsvetkova、Mariana Ninova、Hristo Najdenski

  DOI：10.1016/j.ejmech.2008.05.010

  日期：2009.5

  A large series of chalcones were synthesized and studied against Staphylococcus aureus and Escherichia coli. Chalcones were either unsubstituted in ring A or possessed 4-chloro or 3',4',5'-trimethoxy groups. Their other ring B was variously substituted. It was found that the antistaphylococcal activity of chalcones was related to the energy difference between the two highest occupied molecular orbitals (HOMO and HOMO-1). Presence of hydroxyl group in ring B was not a determinant factor for the anti-staphylococcal activity, but the lipophilicity of ring A of the hydroxyl chalcones was of importance. (C) 2008 Elsevier Masson SAS. All rights reserved.
• 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.