N-(3-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phenyl)-4-methoxybenzamide

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: N-(3-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phenyl)-4-methoxybenzamide
• 英文别名: N-[3-(5-hydroxy-6,7-dimethoxy-4-oxochromen-2-yl)phenyl]-4-methoxybenzamide
• 化学式: C₂₅H₂₁NO₇
• 分子量: 447.444
• InChiKey: ACLWIEYDIDOCFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯酚 在 三氟化硼乙醚 、 碘 、 sodium methylate 、 三氯化硼 、 四氯化锡 、 C.I.酸性橙108 、 三乙胺 、 三甲氧基磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 丙酮 为溶剂， 反应 6.08h， 生成 N-(3-(5-hydroxy-6,7-dimethoxy-4-oxo-4H-chromen-2-yl)phenyl)-4-methoxybenzamide
  参考文献：
  名称：

  天然产物杂化物：3,5,4'-三甲氧基苯乙烯-5,6,7-三甲氧基黄酮嵌合类似物作为针对多种人类癌细胞的潜在细胞毒性剂

  摘要：

  癌症仍然是全球主要的健康问题。当前所有可用的抗癌剂均具有诸如耐药性或副作用之类的缺点。因此，需要引入新型抗癌剂。出于对基于天然产物的药物发现的高成功率的兴趣，我们设计并合成了抗增殖化学实体，将其作为两种天然产物的混合物；3,5,4'-三甲氧基sti和5,6,7-三甲氧基黄酮。为了探测合成化合物的光谱，针对代表主要癌症疾病的九个小组进行了体外评估。结果显示杂化类似物4f，4h，4k和4q作为有前途的广谱抗癌先导化合物，可引起代表多种癌症疾病的几种细胞系的高生长抑制作用。对有前景的先导化合物针对正常人细胞系的评估表明对癌细胞具有选择性的细胞毒性作用。对化合物4f在人宫颈癌HeLa细胞中的细胞毒活性的机理研究表明，它通过诱导凋亡来触发细胞死亡。总体而言，这项研究提出了天然产物杂合类似物4f，4h，4k和4q作为潜在的先导化合物，用于进一步开发新型抗癌疗法。

  DOI：

  10.1016/j.ejmech.2018.10.062

文献信息

• Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells
  作者：Bo Hee Yun、Young Hun Lee、Kyung Tae Park、Su Jin Jung、Yong Sup Lee

  DOI：10.1016/j.bmcl.2016.07.063

  日期：2016.9

  Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI(50) = 7.06 mu M) and MCF-7 (GI(50) = 7.67 mu M) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile. (C) 2016 Elsevier Ltd. All rights reserved.
• Repurposing mosloflavone/5,6,7-trimethoxyflavone-resveratrol hybrids: Discovery of novel p38-α MAPK inhibitors as potent interceptors of macrophage-dependent production of proinflammatory mediators
  作者：Ahmed H.E. Hassan、Sung Yeun Yoo、Kun Won Lee、Yoon Mi Yoon、Hye Won Ryu、Youngdo Jeong、Ji-Sun Shin、Shin-Young Kang、Seo-Yeon Kim、Hwi-Ho Lee、Boyoung Y. Park、Kyung-Tae Lee、Yong Sup Lee

  DOI：10.1016/j.ejmech.2019.07.030

  日期：2019.10

  Herein, we address repurposing hybrids of mosloflavone or 5,6,7-trimethoxyflavone with amide analogs of resveratrol from anticancer leads to novel potent anti-inflammatory chemical entities. To unveil the potent anti-inflammatory molecules, biological evaluations were initiated in LPS-induced RAW 264.7 macrophages at 1 mu M concentration. Promising compounds were further evaluated at various concentrations. Multiple proinflammatory mediators were assessed including NO, PGE(2), IL-6, TNF-alpha and IL-1 beta. Compound 5z inhibited the induced production of NO, PGE(2), IL-6, TNF-alpha and IL-1 beta at the low 1 mu M concentration by 44.76, 35.71, 53.48, 29.39 and 41.02%, respectively. Compound 5z elicited IC50 values as low as 2.11 and 0.98 mu M against NO and PGE(2) production respectively. Compounds 5q and 5g showed potent submicromolar IC50 values of 0.31 and 0.59 mu M respectively against PGE(2) production. Reverse docking of compound 5z suggested p38-alpha MAPK, which is a key signaling molecule within the pathways controlling the transcription of proinflammatory mediators, as the molecular target. Biochemical testing confirmed these compounds as p38-alpha MAPK inhibitors explaining its potent inhibition of proinflammatory mediators' production. Collectively, the results presented 5z as a promising compound for further development of anti-inflammatory agents for treatment of macrophages-and/or immune mediated inflammatory diseases. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Natural products hybrids: 3,5,4′-Trimethoxystilbene-5,6,7-trimethoxyflavone chimeric analogs as potential cytotoxic agents against diverse human cancer cells
  作者：Ahmed H.E. Hassan、Eunwoo Choi、Yoon Mi Yoon、Kun Won Lee、Sung Yeun Yoo、Min Chang Cho、Ji Seul Yang、Hye In Kim、Joo Young Hong、Ji-Sun Shin、Kyung-Sook Chung、Jeong-Hun Lee、Kyung-Tae Lee、Yong Sup Lee

  DOI：10.1016/j.ejmech.2018.10.062

  日期：2019.1

  conducted against nine panels representing major cancer diseases. The results revealed the hybrid analogs 4f, 4h, 4k and 4q as promising broad-spectrum anticancer lead compounds eliciting high growth inhibition of several cell lines representing multiple cancers diseases. Evaluation of the promising lead compounds against normal human cell lines suggested a selective cytotoxic effect on cancer cells.

  癌症仍然是全球主要的健康问题。当前所有可用的抗癌剂均具有诸如耐药性或副作用之类的缺点。因此，需要引入新型抗癌剂。出于对基于天然产物的药物发现的高成功率的兴趣，我们设计并合成了抗增殖化学实体，将其作为两种天然产物的混合物；3,5,4'-三甲氧基sti和5,6,7-三甲氧基黄酮。为了探测合成化合物的光谱，针对代表主要癌症疾病的九个小组进行了体外评估。结果显示杂化类似物4f，4h，4k和4q作为有前途的广谱抗癌先导化合物，可引起代表多种癌症疾病的几种细胞系的高生长抑制作用。对有前景的先导化合物针对正常人细胞系的评估表明对癌细胞具有选择性的细胞毒性作用。对化合物4f在人宫颈癌HeLa细胞中的细胞毒活性的机理研究表明，它通过诱导凋亡来触发细胞死亡。总体而言，这项研究提出了天然产物杂合类似物4f，4h，4k和4q作为潜在的先导化合物，用于进一步开发新型抗癌疗法。