(2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4,6-trimethoxyphenyl)-2-propen-1-one | 290332-36-4

• 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: (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4,6-trimethoxyphenyl)-2-propen-1-one
• 英文别名: (E)-1-(3,4,5-trimethoxyphenyl)-3-(2,4,6-trimethoxyphenyl)prop-2-en-1-one；(E)-3-(2,4,6-trimethoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 290332-36-4
• 化学式: C₂₁H₂₄O₇
• 分子量: 388.417
• InChiKey: BLCLZMXNVIYXEW-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 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：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4,6-trimethoxyphenyl)-2-propen-1-one 、 硫脲 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 生成 4-(2,4,6-trimethoxyphenyl)-6-(3,4,5-trimethoxyphenyl)-3,4-dihydro-1H-pyrimidine-2-thione
  参考文献：
  名称：

  1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4

  摘要：

  Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity IC50 <1 mu M for L1210 and <10 mu M for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 mu M, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity. (C) 2007 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2007.11.030
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 、 2,4,6-三甲氧基苯甲醛 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以20%的产率得到(2E)-1-(3',4',5'-trimethoxyphenyl)-3-(2,4,6-trimethoxyphenyl)-2-propen-1-one
  参考文献：
  名称：

  Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors

  摘要：

  Based on classical colchicine site ligands and a computational model of the colchicine binding site on beta tubulin, two classes of chalcone derivatives were designed, synthesized and evaluated for inhibition of tubulin assembly and toxicity in human cancer cell lines. Docking studies suggested that the chalcone scaffold could fit the colchicine site on tubulin in an orientation similar to that of the natural product. In particular, a 3,4,5-trimethoxyphenyl ring adjacent to the carbonyl group appeared to benefit the ligand-tubulin interaction, occupying the same subcavity as the corresponding moiety in colchicine. Consistent with modeling predictions, several 3,4,5-trimethoxychalcones showed improved cytotoxicity to murine acute lymphoblastic leukemia cells compared with a previously described parent compound, and inhibited tubulin assembly in vitro as potently as colchicine. The most potent chalcones inhibited the growth of human leukemia cell lines at nanomolar concentrations, caused microtubule destabilization and mitotic arrest in human cervical cancer cells, and inhibited human breast cancer cell migration in scratch wound and Boyden chamber assays. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.037

文献信息

• Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity
  作者：Sylvie Ducki、David Rennison、Meiko Woo、Alexander Kendall、Jérémie Fournier Dit Chabert、Alan T. McGown、Nicholas J. Lawrence

  DOI：10.1016/j.bmc.2009.09.039

  日期：2009.11

  The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 mu M; CA4, 0.10 mu M) and compete with [H-3] colchicine for binding to tubulin (8% [H-3] colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity. (C) 2009 Elsevier Ltd. All rights reserved.
• Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors
  作者：Lívia B. Salum、Wanessa F. Altei、Louise D. Chiaradia、Marlon N.S. Cordeiro、Rafael R. Canevarolo、Carolina P.S. Melo、Evelyn Winter、Bruno Mattei、Hikmat N. Daghestani、Maria Cláudia Santos-Silva、Tânia B. Creczynski-Pasa、Rosendo A. Yunes、José A. Yunes、Adriano D. Andricopulo、Billy W. Day、Ricardo J. Nunes、Andreas Vogt

  DOI：10.1016/j.ejmech.2013.02.037

  日期：2013.5

  Based on classical colchicine site ligands and a computational model of the colchicine binding site on beta tubulin, two classes of chalcone derivatives were designed, synthesized and evaluated for inhibition of tubulin assembly and toxicity in human cancer cell lines. Docking studies suggested that the chalcone scaffold could fit the colchicine site on tubulin in an orientation similar to that of the natural product. In particular, a 3,4,5-trimethoxyphenyl ring adjacent to the carbonyl group appeared to benefit the ligand-tubulin interaction, occupying the same subcavity as the corresponding moiety in colchicine. Consistent with modeling predictions, several 3,4,5-trimethoxychalcones showed improved cytotoxicity to murine acute lymphoblastic leukemia cells compared with a previously described parent compound, and inhibited tubulin assembly in vitro as potently as colchicine. The most potent chalcones inhibited the growth of human leukemia cell lines at nanomolar concentrations, caused microtubule destabilization and mitotic arrest in human cervical cancer cells, and inhibited human breast cancer cell migration in scratch wound and Boyden chamber assays. (C) 2013 Elsevier Masson SAS. All rights reserved.
• 1,2,3,4-Tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4
  作者：Lauren Lee、Ryan Davis、Jenna Vanderham、Patrice Hills、Hilary Mackay、Toni Brown、Susan L. Mooberry、Moses Lee

  DOI：10.1016/j.ejmech.2007.11.030

  日期：2008.9

  Eleven 1,2,3,4-tetrahydro-2-thioxopyrimidine analogs of combretastatin-A4 (CA-4) were synthesized and their cytotoxicity against the growth of two murine cancer cell lines (B16 melanoma and L1210 leukemia) in culture was determined using an MTT assay. Two 2-thioxopyrimidine analogs 8f and 9a exhibited significant activity IC50 <1 mu M for L1210 and <10 mu M for B16 cells). Exposure of A-10 cells to 8f and 9a produced a significant reduction in cellular microtubules in interphase cells, with an EC50 value of 4.4 and 2.9 mu M, respectively, for microtubule loss. Molecular modeling studies using MacSpartan indicated that the two active 2-thioxopyrimidine analogs preferably adopt a twisted conformation, similar to CA-4, affirming that conformation and structure are connected to activity. (C) 2007 Elsevier Masson SAS. All rights reserved.