(2E)-1-(3',4',5'-trimethoxyphenyl)-3-(5-methylfuran-2-yl)-2-propen-1-one | 1442690-91-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(5-methylfuran-2-yl)-2-propen-1-one
• 英文别名: (E)-3-(5-methylfuran-2-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 1442690-91-6
• 化学式: C₁₇H₁₈O₅
• 分子量: 302.327
• InChiKey: RFFHSFLLPNEBDF-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-甲基呋喃醛 、 3',4',5'-三甲氧基苯乙酮 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以78%的产率得到(2E)-1-(3',4',5'-trimethoxyphenyl)-3-(5-methylfuran-2-yl)-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

• 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.
• Synthetic compounds from an <i>in house</i> library as inhibitors of falcipain-2 from <i>Plasmodium falciparum</i>
  作者：Jean Borges Bertoldo、Louise Domeneghini Chiaradia-Delatorre、Alessandra Mascarello、Paulo César Leal、Marlon Norberto Sechini Cordeiro、Ricardo José Nunes、Emir Salas Sarduy、Philip Jon Rosenthal、Hernán Terenzi

  DOI：10.3109/14756366.2014.920839

  日期：2015.3.4

  Falcipain-2 (FP-2) is a key cysteine protease from the malaria parasite Plasmodium falciparum. Many previous studies have identified FP-2 inhibitors; however, none has yet met the criteria for an antimalarial drug candidate. In this work, we assayed an in-house library of non-peptidic organic compounds, including (E)-chalcones, (E)-N'-benzylidene-benzohydrazides and alkylesters of gallic acid, and assessed the activity toward FP-2 and their mechanisms of inhibition. The (E)-chalcones 48, 54 and 66 showed the lowest IC50 values (8.5 +/- 0.8 mu M, 9.5 +/- 0.2 mu M and 4.9 +/- 1.3 mu M, respectively). The best inhibitor (compound 66) demonstrated non-competitive inhibition, and using mass spectrometry and fluorescence spectroscopy assays, we suggest a potential allosteric site for the interaction of this compound, located between the catalytic site and the hemoglobin binding arm in FP-2. We combined structural biology tools and mass spectrometry to characterize the inhibition mechanisms of novel compounds targeting FP-2.