2,4,6-trihydroxy-3-geranylacetophenone | 213892-83-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,4,6-trihydroxy-3-geranylacetophenone
• 英文别名: tHGA；1-[3-(3,7-Dimethylocta-2,6-dienyl)-2,4,6-trihydroxyphenyl]ethanone；1-[3-(3,7-dimethylocta-2,6-dienyl)-2,4,6-trihydroxyphenyl]ethanone
• CAS: 213892-83-2
• 化学式: C₁₈H₂₄O₄
• 分子量: 304.386
• InChiKey: RCOXTTLIGHDQHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  77.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  geranyl bromide 、 2,4,6-三羟基苯乙酮一水合物 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 生成 2,4,6-trihydroxy-3-geranylacetophenone
  参考文献：
  名称：

  Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry

  摘要：

  2,4,6-三羟基-3-香叶酰丙酮（tHGA）是一种生物活性化合物，具有出色的抗炎特性。然而，它的药代动力学和代谢尚未得到评估。本研究开发并验证了一种敏感的LC-HRMS方法，用于定量大鼠血浆中的tHGA。该方法显示了良好的线性（0.5-80 ng/mL）。准确性和精密度均在10％以内。对三组六只大鼠进行了药代动力学研究。前两组分别口服未配制和脂质体包封的tHGA，而第三组接受腹腔注射脂质体包封的tHGA。腹腔注射的Cmax，达到Cmax所需的时间（tmax），消除半衰期（t1/2）和曲线下面积（AUC0-24）值分别为54.6 ng/mL，1.5小时，6.7小时和193.9 ng/mL·h。对于未配制和配制的tHGA的口服给药，Cmax值分别为5.4和14.5 ng/mL，tmax值均为0.25小时，t1/2值分别为6.9和6.6小时，AUC0-24值分别为17.6和40.7 ng/mL·h。脂质体配方将tHGA的相对口服生物利用度从9.1％提高到21.0％，增加了2.3倍。此外，检测到并结构化了12种代谢物。代谢物主要是氧化和葡萄糖醛酸结合的产物。

  DOI：

  10.3390/molecules25133069

文献信息

• Barrier protective effects of 2,4,6-trihydroxy-3-geranyl acetophenone on lipopolysaccharides-stimulated inflammatory responses in human umbilical vein endothelial cells
  作者：Yi Joong Chong、Nazmi Firdaus Musa、Chean Hui Ng、Khozirah Shaari、Daud Ahmad Israf、Chau Ling Tham

  DOI：10.1016/j.jep.2016.07.032

  日期：2016.11

  Pharmacological relevance: 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), is a phloroglucinol compound found naturally in Melicope ptelefolia. Melicope ptelefolia has been used traditionally for centuries as natural remedy for wound infections and inflammatory diseases.Aim of the study: Endothelial barrier dysfunction is a pathological hallmark of many diseases and can be caused by lipopolysaccharides (LPS) stimulation. Therefore, this study aims to investigate the possible barrier protective effects of tHGA upon LPS-stimulated inflammatory responses in human umbilical vein endothelial cells (HUVECs).Materials and methods: HUVECs were pretreated with tHGA prior to LPS stimulation, where inflammatory parameters including permeability, monocyte adhesion and migration, and release of pro inflammatory mediators were examined. Additionally, the effect of tHGA on F-actin rearrangement and adhesion protein expression of LPS-stimulated HUVECs was evaluated.Results: It-was found that pretreatment with tHGA inhibited monocyte-adhesion and transendothelial migration, reduced endothelial hyperpermeability and secretion of prostaglandin E-2 (PGE(2)). Additionally, tHGA inhibited cytoskeletal rearrangement and adhesion protein expression on LPS-stimulated HUVECs.Conclusion: As the regulation of endothelial barrier dysfunction can be one of the therapeutic strategies to improve the outcome of inflammation, tHGA may be able to preserve vascular barrier integrity of endothelial cells following LPS-stimulated dysfunction, thereby endorsing its potential usefulness in vascular inflammatory diseases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
• Pharmacokinetics and Metabolism of Liposome-Encapsulated 2,4,6-Trihydroxygeranylacetophenone in Rats Using High-Resolution Orbitrap Liquid Chromatography Mass Spectrometry
  作者：Yamen Alkhateeb、Qais Bashir Jarrar、Faridah Abas、Yaya Rukayadi、Chau Ling Tham、Yuen Kah Hay、Khozirah Shaari

  DOI：10.3390/molecules25133069

  日期：——

  2,4,6-trihydroxy-3-geranylacetophenone (tHGA) is a bioactive compound that shows excellent anti-inflammatory properties. However, its pharmacokinetics and metabolism have yet to be evaluated. In this study, a sensitive LC-HRMS method was developed and validated to quantify tHGA in rat plasma. The method showed good linearity (0.5–80 ng/mL). The accuracy and precision were within 10%. Pharmacokinetic investigations were performed on three groups of six rats. The first two groups were given oral administrations of unformulated and liposome-encapsulated tHGA, respectively, while the third group received intraperitoneal administration of liposome-encapsulated tHGA. The maximum concentration (Cmax), the time required to reach Cmax (tmax), elimination half-life (t1/2) and area under curve (AUC0–24) values for intraperitoneal administration were 54.6 ng/mL, 1.5 h, 6.7 h, and 193.9 ng/mL·h, respectively. For the oral administration of unformulated and formulated tHGA, Cmax values were 5.4 and 14.5 ng/mL, tmax values were 0.25 h for both, t1/2 values were 6.9 and 6.6 h, and AUC0–24 values were 17.6 and 40.7 ng/mL·h, respectively. The liposomal formulation improved the relative oral bioavailability of tHGA from 9.1% to 21.0% which was a 2.3-fold increment. Further, a total of 12 metabolites were detected and structurally characterized. The metabolites were mainly products of oxidation and glucuronide conjugation.

  2,4,6-三羟基-3-香叶酰丙酮（tHGA）是一种生物活性化合物，具有出色的抗炎特性。然而，它的药代动力学和代谢尚未得到评估。本研究开发并验证了一种敏感的LC-HRMS方法，用于定量大鼠血浆中的tHGA。该方法显示了良好的线性（0.5-80 ng/mL）。准确性和精密度均在10％以内。对三组六只大鼠进行了药代动力学研究。前两组分别口服未配制和脂质体包封的tHGA，而第三组接受腹腔注射脂质体包封的tHGA。腹腔注射的Cmax，达到Cmax所需的时间（tmax），消除半衰期（t1/2）和曲线下面积（AUC0-24）值分别为54.6 ng/mL，1.5小时，6.7小时和193.9 ng/mL·h。对于未配制和配制的tHGA的口服给药，Cmax值分别为5.4和14.5 ng/mL，tmax值均为0.25小时，t1/2值分别为6.9和6.6小时，AUC0-24值分别为17.6和40.7 ng/mL·h。脂质体配方将tHGA的相对口服生物利用度从9.1％提高到21.0％，增加了2.3倍。此外，检测到并结构化了12种代谢物。代谢物主要是氧化和葡萄糖醛酸结合的产物。