3-(6'-bromohexyloxy)-4-hydroxy-9H-xanthen-9-one | 1187388-92-6

• 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: 3-(6'-bromohexyloxy)-4-hydroxy-9H-xanthen-9-one
• 英文别名: 3-(6-Bromohexoxy)-4-hydroxyxanthen-9-one
• CAS: 1187388-92-6
• 化学式: C₁₉H₁₉BrO₄
• 分子量: 391.261
• InChiKey: YXXPWFJTAXBXEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 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 3-(6'-bromohexyloxy)-4-hydroxy-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

• Bromoalkoxyxanthones as promising antitumor agents: Synthesis, crystal structure and effect on human tumor cell lines
  作者：Emília Sousa、Ana Paiva、Nair Nazareth、Luis Gales、Ana M. Damas、Maria S.J. Nascimento、Madalena Pinto

  DOI：10.1016/j.ejmech.2009.04.011

  日期：2009.9

  In a study involving the synthesis of bis-intercalators, a bisxanthone and a minor product, 1-(6-bromohexyloxy)-xanthone were obtained. Although no capacity to inhibit the growth of human tumor cell lines was observed for the bisxanthone, the bromoalkoxyxanthone revealed this biological activity. In light of these results bromoalkylation of 3,4-dihydroxyxanthone furnished two bromohexyloxyxanthones that were investigated for their effect on the in vitro growth of human tumor cell lines MCF-7 (ER+, breast), MDA-MB-231 (ER-, breast), NCI-H460 (non-small lung), and SF-268 (central nervous system). The X-ray structure of 1-(6-bromohexyloxy)-xanthone revealed that the xanthone skeleton remains essentially planar forming a dihedral angle of 61.3(2)degrees with the 6-bromohexyl side chain. These results revealed bromoalkoxyxanthones as interesting scaffolds to look for potential anticancer drugs. (C) 2009 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.