1,2-bis((3-methylbut-2-en-1-yl)oxy)-9H-xanthen-9-one | 1241391-93-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1,2-bis((3-methylbut-2-en-1-yl)oxy)-9H-xanthen-9-one
• 英文别名: 3,4-bis(3-methylbut-2-enyloxy)-9H-xanthen-9-one；3,4-Bis(3-methylbut-2-enoxy)xanthen-9-one
• CAS: 1241391-93-4
• 化学式: C₂₃H₂₄O₄
• 分子量: 364.441
• InChiKey: WMRCBHCWDRAHPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,4-dimethoxyxanthen-9-one 在 aluminum (III) chloride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.0h， 生成 1,2-bis((3-methylbut-2-en-1-yl)oxy)-9H-xanthen-9-one
  参考文献：
  名称：

  Insights into the In Vitro Antitumor Mechanism of Action of a New Pyranoxanthone

  摘要：

  Naturally occurring xanthones have been documented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other molecular modifications were performed. All the compounds reduced viable cell number in a leukemia cell line K‐562, with the fused xanthone 3,4‐dihydro‐12‐hydroxy‐2,2‐dimethyl‐2H,6H‐pyrano[3,2‐b]xanthen‐6‐one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL‐60 and BV‐173). Furthermore, the pyranoxanthone 5 decreased cellular proliferation and induced an S‐phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a computer screening strategy based on the structure of several anti‐ and pro‐apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti‐apoptotic Bcl‐xL to pro‐apoptotic Bad and Bim. The structure‐based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl‐xL.

  DOI：

  10.1111/j.1747-0285.2010.00978.x

文献信息

• Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives
  作者：Ralph Urbatzka、Sara Freitas、Andreia Palmeira、Tiago Almeida、João Moreira、Carlos Azevedo、Carlos Afonso、Marta Correia-da-Silva、Emilia Sousa、Madalena Pinto、Vitor Vasconcelos

  DOI：10.1016/j.ejmech.2018.03.036

  日期：2018.5

  Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 mu M with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 mu M in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. (C) 2018 Elsevier Masson SAS. All rights reserved.
• Insights into the In Vitro Antitumor Mechanism of Action of a New Pyranoxanthone
  作者：Andreia Palmeira、Ana Paiva、Emília Sousa、Hugo Seca、Gabriela M. Almeida、Raquel T. Lima、Miguel X. Fernandes、Madalena Pinto、M. Helena Vasconcelos

  DOI：10.1111/j.1747-0285.2010.00978.x

  日期：——

  Naturally occurring xanthones have been documented as having antitumor properties, with some of them presently undergoing clinical trials. In an attempt to improve the biological activities of dihydroxyxanthones, prenylation and other molecular modifications were performed. All the compounds reduced viable cell number in a leukemia cell line K‐562, with the fused xanthone 3,4‐dihydro‐12‐hydroxy‐2,2‐dimethyl‐2H,6H‐pyrano[3,2‐b]xanthen‐6‐one (5) being the most potent. The pyranoxanthone 5 was particularly effective in additional leukemia cell lines (HL‐60 and BV‐173). Furthermore, the pyranoxanthone 5 decreased cellular proliferation and induced an S‐phase cell cycle arrest. In vitro, the pyranoxanthone 5 increased the percentage of apoptotic cells which was confirmed by an appropriate response at the protein level (e.g., PARP cleavage). Using a computer screening strategy based on the structure of several anti‐ and pro‐apoptotic proteins, it was verified that the pyranoxanthone 5 may block the binding of anti‐apoptotic Bcl‐xL to pro‐apoptotic Bad and Bim. The structure‐based screening revealed the pyranoxanthone 5 as a new scaffold that may guide the design of small molecules with better affinity profile for Bcl‐xL.