6-((1’E,3’E,5’E,7’E)-8’-(3-chloro-1H-pyrrol-2-yl)octa-1,3,5,7-tetraenyl)-4-hydroxy-2H-pyran-2-one | 1255529-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: 6-((1’E,3’E,5’E,7’E)-8’-(3-chloro-1H-pyrrol-2-yl)octa-1,3,5,7-tetraenyl)-4-hydroxy-2H-pyran-2-one
• 英文别名: 4-hydroxy auxarconjugatin B；6-((1E,3E,5E,7E)-8-(3-chloro-1H-pyrrol-2-yl)octa-1,3,5,7-tetraenyl)-4-hydroxy-2H-pyran-2-one；6-[(1E,3E,5E,7E)-8-(3-chloro-1H-pyrrol-2-yl)octa-1,3,5,7-tetraenyl]-4-hydroxypyran-2-one
• CAS: 1255529-12-4
• 化学式: C₁₇H₁₄ClNO₃
• 分子量: 315.756
• InChiKey: GWPAXNCZXNDYMI-QEQQUMNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-(2-bromovinyl)-3-chloro-1-(methylsulfonyl)-1H-pyrrole 、 4-hydroxy-6-((1E,3E,5E)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)hexa-1,3,5-trienyl)-2H-pyran-2-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三苯胂 、 potassium hydroxide 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.92h， 生成 6-((1’E,3’E,5’E,7’E)-8’-(3-chloro-1H-pyrrol-2-yl)octa-1,3,5,7-tetraenyl)-4-hydroxy-2H-pyran-2-one
  参考文献：
  名称：

  Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome

  摘要：

  痛风性关节炎是由关节内尿酸结晶的产生引起的。这些尿酸晶体会激活NACHT、LRR和PYD结构域蛋白3（NLRP3）炎症小体，该小体参与慢性炎症性疾病，包括痛风性关节炎。本研究发现了一种新的自噬诱导剂多烯基吡咯衍生物4-羟基奥克萨康胶原素B（4-HAB），该剂量减弱了体内外尿酸晶体介导的NLRP3炎症小体激活。4-HAB剂量依赖性地降低了尿酸晶体激活的巨噬细胞中白细胞介素（IL）-1β、IL-18、活性半胱氨酸酶-1和凋亡相关斑点样蛋白（ASC）的释放。在机械研究中，4-HAB被证明能够抑制尿酸晶体诱导的线粒体损伤、溶酶体破裂和ASC寡聚化。此外，4-HAB通过Sirt1依赖的自噬诱导抑制NLRP3炎症小体。此外，在尿酸晶体介导的腹膜炎小鼠模型中，4-HAB的抗炎特性通过灌洗液中中性粒细胞浸润、IL-1β、活性半胱氨酸酶-1、IL-6和MCP-1的降低得到确认。总之，4-HAB通过抑制Sirt1/自噬诱导途径减轻痛风性炎症。

  DOI：

  10.3390/cells9020279

文献信息

• Synthesis and Biological Evaluation of Polyenylpyrrole Derivatives as Anticancer Agents Acting through Caspases-Dependent Apoptosis
  作者：Zhanxiong Fang、Pei-Chun Liao、Yu-Liang Yang、Feng-Ling Yang、Yi-Lin Chen、Yulin Lam、Kuo-Feng Hua、Shih-Hsiung Wu

  DOI：10.1021/jm100619x

  日期：2010.11.25

  A class of polyenylpyrroles and their analogues were designed from a hit compound identified in a fungus. The compounds synthesized were evaluated for their cell cytotoxicity against human non-small-cell lung carcinoma cell lines A549. Two compounds were found to exhibit high cytotoxicity against A549 cells with IC50 of 0.6 and 0.01 mu M, respectively. The underlying mechanisms for the anticancer activity were demonstrated as caspases activation dependent apoptosis induction through loss of mitochondrial membrane potential, release of cytochrome c, increase in B-cell lymphoma-2-associated X protein (Bax) level, and decrease in B-cell lymphoma-2 (Bcl-2) level. The two compounds were nontoxic to normal human lung Beas-2b cells (IC50 > 80 mu M), indicating that they are highly selective in their cytotoxicity activities. Furthermore, one compound showed in vivo anticancer activity in human-lung-cancer-cell-bearing mice. These results open promising insights on how these conjugated polyenes mediate cytotoxicity and may provide a molecular rationale for future therapeutic interventions in carcinogenesis.
• USE OF POLYENYLPYRROLE DERIVATIVES FOR TREATING INFLAMMATION
  申请人：LEE Yu-Chieh

  公开号：US20150284355A1

  公开（公告）日：2015-10-08

  The preset invention relates to a method for treating inflammation comprising administering a subject in need thereof with a therapeutically effective amount of polyenylpyrrole derivatives of formula (I) or a pharmaceutically acceptable salt thereof.
• US9475789B2
  申请人：——

  公开号：US9475789B2

  公开（公告）日：2016-10-25
• Synthetic 4-Hydroxy Auxarconjugatin B, a Novel Autophagy Inducer, Attenuates Gouty Inflammation by Inhibiting the NLRP3 Inflammasome
  作者：Chih-Yu Hsieh、Lan-Hui Li、Yulin Lam、Zhanxiong Fang、Chin Heng Gan、Yerra Koteswara Rao、Hsiao-Wen Chiu、Wei-Ting Wong、Tz-Chuen Ju、Fang-Hsin Chen、Oleg V. Chernikov、May-Lan Liu、Chung-Hua Hsu、Kuo-Feng Hua

  DOI：10.3390/cells9020279

  日期：——

  Gouty arthritis results from the generation of uric acid crystals within the joints. These uric acid crystals activate the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, which is involved in chronic inflammatory diseases, including gouty arthritis. This study identified the polyenylpyrrole derivative 4-hydroxy auxarconjugatin B (4-HAB), a novel autophagy inducer, which attenuated uric acid crystals-mediated activation of the NLRP3 inflammasome in vitro and in vivo. 4-HAB dose-dependently reduced the release of interleukin (IL)-1β, IL-18, active caspase-1 and apoptosis-associated speck-like protein (ASC) in uric acid crystals-activated macrophages. In a mechanistic study, 4-HAB was shown to inhibit uric acid crystals-induced mitochondrial damage, lysosomal rupture and ASC oligomerization. Additionally, 4-HAB inhibited the NLRP3 inflammasome through Sirt1-dependent autophagy induction. Furthermore, the anti-inflammatory properties of 4-HAB were confirmed in a mouse model of uric acid crystals-mediated peritonitis by the reduced levels of neutrophil influx, IL-1β, active caspase-1, IL-6 and MCP-1 in lavage fluids. In conclusion, 4-HAB attenuates gouty inflammation, in part by attenuating activation of the NLRP3 inflammasome through the Sirt1/autophagy induction pathway.

  痛风性关节炎是由关节内尿酸结晶的产生引起的。这些尿酸晶体会激活NACHT、LRR和PYD结构域蛋白3（NLRP3）炎症小体，该小体参与慢性炎症性疾病，包括痛风性关节炎。本研究发现了一种新的自噬诱导剂多烯基吡咯衍生物4-羟基奥克萨康胶原素B（4-HAB），该剂量减弱了体内外尿酸晶体介导的NLRP3炎症小体激活。4-HAB剂量依赖性地降低了尿酸晶体激活的巨噬细胞中白细胞介素（IL）-1β、IL-18、活性半胱氨酸酶-1和凋亡相关斑点样蛋白（ASC）的释放。在机械研究中，4-HAB被证明能够抑制尿酸晶体诱导的线粒体损伤、溶酶体破裂和ASC寡聚化。此外，4-HAB通过Sirt1依赖的自噬诱导抑制NLRP3炎症小体。此外，在尿酸晶体介导的腹膜炎小鼠模型中，4-HAB的抗炎特性通过灌洗液中中性粒细胞浸润、IL-1β、活性半胱氨酸酶-1、IL-6和MCP-1的降低得到确认。总之，4-HAB通过抑制Sirt1/自噬诱导途径减轻痛风性炎症。