(2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one | 1098176-72-7

• 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: (2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one
• 英文别名: (2E)-1-(3'-methoxy-4'-hydroxyphenyl)-3-(2-naphthyl)-2-propen-1-one；1-(4-Hydroxy-3-methoxyphenyl)-3-(naphthalen-2-yl)prop-2-en-1-one；(E)-1-(4-hydroxy-3-methoxyphenyl)-3-naphthalen-2-ylprop-2-en-1-one
• CAS: 1098176-72-7
• 化学式: C₂₀H₁₆O₃
• 分子量: 304.345
• InChiKey: OAGVNDJNFSRJHP-JXMROGBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-萘甲醛 、 香草乙酮 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以39%的产率得到(2E)-3-(2-naphthyl)-1-(3'-methoxy-4'-hydroxy-phenyl)-2-propen-1-one
  参考文献：
  名称：

  Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic leukaemia cells by (2E)-3-(2-naphthyl)-1-(3′-methoxy-4′-hydroxy-phenyl)-2-propen-1-one

  摘要：

  对于癌症治疗，需要具有生物靶点且对正常细胞毒性较小的新化合物。本研究评估了从2-萘醛衍生的十种合成查尔酮对小鼠急性淋巴细胞白血病细胞L-1210的细胞毒性作用。

  通过用甲醇作为溶剂，在基础条件下，于室温下进行24小时的醛缩反应，制备了十种从2-萘醛和相应的苯乙酮衍生的查尔酮。细胞活力通过MTT比色法确定。细胞周期分析通过丙磷碘化物染色后的流式细胞术进行。通过暴露于磷脂酰丝氨酸（ANNEXIN V-FITC）评估凋亡诱导。通过细胞仪分析评估p53、Bcl-2和Bax蛋白的表达。通过免疫印迹分析研究caspase-3的表达。

  对从2-萘醛衍生的十种查尔酮进行初步筛选显示，查尔酮8，(2E)-3-(2-萘基)-1-(3′-甲氧基-4′-羟基苯基)-2-丙烯-1-酮，具有最高的细胞毒性作用（IC50为54 µm），但对正常人淋巴细胞无影响。为了更好地理解查尔酮8的细胞毒性机制，评估了其对细胞周期和凋亡的影响。我们的结果显示，查尔酮8导致细胞周期在G2/M期的停滞，并显著增加了处于亚G0/G1期的细胞比例。我们的结果还表明，查尔酮8促进了Bax:Bcl-2比率的改变，增加了p53的表达和caspase-3的活化。

  研究的查尔酮8对L-1210淋巴细胞白血病细胞具有细胞毒性作用，这种作用与p-53和Bax表达的增加有关。

  DOI：

  10.1111/j.2042-7158.2010.01141.x

文献信息

• Induction of apoptosis and cell cycle arrest in L-1210 murine lymphoblastic leukaemia cells by (2<i>E</i>)-3-(2-naphthyl)-1-(3′-methoxy-4′-hydroxy-phenyl)-2-propen-1-one
  作者：Fernanda Spezia Pedrini、Louise Domeneghini Chiaradia、Marley Aparecida Licínio、Ana Carolina Rabello De Moraes、Juliana Costa Curta、Aline Costa、Alessandra Mascarello、Tânia Beatriz Creczinsky-Pasa、Ricardo José Nunes、Rosendo Augusto Yunes、Maria Cláudia Santos-Silva

  DOI：10.1111/j.2042-7158.2010.01141.x

  日期：2010.8.2

  New compounds with biological targets and less cytotoxicity to normal cells are necessary for cancer therapy. In this work ten synthetic chalcones derived from 2-naphtaldehyde were evaluated for their cytotoxic effect in murine acute lymphoblastic leukemia cells L-1210.

  A series of ten chalcones derived from 2-naphtaldehyde and corresponding acetophenones were prepared by aldolic condensation, using methanol as solvent under basic conditions, at room temperature for 24 h. The cell viability was determined by MTT colorimeter method. The cell cycle phase analysis was carried out by flow cytometry after propidium iodide staining. The apoptosis induction was assessed by exposure to phosphatidylserine (ANNEXIN V-FITC). Cytometric analysis was performed to evaluate the expression of p53, Bcl-2 and Bax protein. The caspase-3 expression was studied by immunoblotting analysis.

  A preliminary screening of a series of ten chalcones derived from 2-naphtaldehyde showed that chalcone 8, (2E)-3-(2-naphtyl)-1-(3′-methoxy-4′-hydroxy-phenyl)-2-propen-1-one, had the highest cytotoxic effect (IC50 of 54 µm), but not in normal human lymphocytes. To better understand the cytotoxic mechanism of chalcone 8, its effect on cell cycle and apoptosis was assessed. Our results showed that chalcone 8 caused cell cycle arrest in the G2/M phase and a significant increase in the proportion of cells in the subG0/G1 phase. Our results also demonstrated that chalcone 8 promoted a modification in Bax : Bcl-2 ratio and increased p53 expression and caspase-3 activation.

  The studied chalcone 8 has cytotoxic effect against L-1210 lymphoblastic leukaemic cells, and this effect is associated with increase of p-53 and Bax expression.

  对于癌症治疗，需要具有生物靶点且对正常细胞毒性较小的新化合物。本研究评估了从2-萘醛衍生的十种合成查尔酮对小鼠急性淋巴细胞白血病细胞L-1210的细胞毒性作用。

  通过用甲醇作为溶剂，在基础条件下，于室温下进行24小时的醛缩反应，制备了十种从2-萘醛和相应的苯乙酮衍生的查尔酮。细胞活力通过MTT比色法确定。细胞周期分析通过丙磷碘化物染色后的流式细胞术进行。通过暴露于磷脂酰丝氨酸（ANNEXIN V-FITC）评估凋亡诱导。通过细胞仪分析评估p53、Bcl-2和Bax蛋白的表达。通过免疫印迹分析研究caspase-3的表达。

  对从2-萘醛衍生的十种查尔酮进行初步筛选显示，查尔酮8，(2E)-3-(2-萘基)-1-(3′-甲氧基-4′-羟基苯基)-2-丙烯-1-酮，具有最高的细胞毒性作用（IC50为54 µm），但对正常人淋巴细胞无影响。为了更好地理解查尔酮8的细胞毒性机制，评估了其对细胞周期和凋亡的影响。我们的结果显示，查尔酮8导致细胞周期在G2/M期的停滞，并显著增加了处于亚G0/G1期的细胞比例。我们的结果还表明，查尔酮8促进了Bax:Bcl-2比率的改变，增加了p53的表达和caspase-3的活化。

  研究的查尔酮8对L-1210淋巴细胞白血病细胞具有细胞毒性作用，这种作用与p-53和Bax表达的增加有关。

• Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA
  作者：Louise Domeneghini Chiaradia、Alessandra Mascarello、Marcela Purificação、Javier Vernal、Marlon Norberto Sechini Cordeiro、María Emilia Zenteno、Andréa Villarino、Ricardo José Nunes、Rosendo Augusto Yunes、Hernán Terenzi

  DOI：10.1016/j.bmcl.2008.09.105

  日期：2008.12

  In the search for lead compounds for new drugs for tuberculosis, the activity of 38 synthetic chalcones were assayed for their potential inhibitory action towards a protein tyrosine phosphatase from Mycobacterium tuberculosis - PtpA. The compounds were obtained by aldolic condensation between aldehydes and acetophenones, under basic conditions. Five compounds presented moderate or good activity. The structure - activity analysis reveals that the predominant factor for the activity is the molecule planarity/hydrophobicity and the nature of the substituents. (C) 2008 Elsevier Ltd. All rights reserved.
• Hydroxychalcones induce apoptosis in B16-F10 melanoma cells via GSH and ATP depletion
  作者：Andréia Lilian Formento Navarini、Louise Domeneghini Chiaradia、Alessandra Mascarello、Márcio Fritzen、Ricardo José Nunes、Rosendo Augusto Yunes、Tânia Beatriz Creczynski-Pasa

  DOI：10.1016/j.ejmech.2008.09.009

  日期：2009.4

  Searching for leading compounds of new drugs for cancer therapy, we studied the toxicity of 13 hydroxychalcones never tested before toward melanoma cell line (B16-F10). The compounds were obtained by aldolic condensation between aldehydes and hydroxylated acetophenones, in alkaline conditions. Three of them showed cytotoxicity to the cell line. Two of them induced mitochondrial GSH and ATP depletion and promoted cell death through apoptosis in melanoma cells. One of the compounds induced cell death through necrosis but did not significantly decrease the intracellular mitochondrial GSH and ATP levels in melanoma cells. The results suggest that the predominant factor for the activity is the molecule shape, and secondarily the number of hydroxyl groups. (c) 2008 Published by Elsevier Masson SAS.
• 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.