3,19-O-diacetyl-14-deoxy-14,15-didehydroandrographolide | 42895-62-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3,19-O-diacetyl-14-deoxy-14,15-didehydroandrographolide
• 英文别名: (E)-(2-acetoxy-1,4a-dimethyl-6-methylene-5-(2-(2-oxofuran-3(2H)-ylidene)ethyl)decahydronaphthalen-1-yl)methyl acetate；3,19-O-diacetylanhydroandrographolide；anhydro-andrographolide diacetate；[(1R,2R,4aS,5R,8aS)-2-acetyloxy-1,4a-dimethyl-6-methylidene-5-[(2E)-2-(2-oxofuran-3-ylidene)ethyl]-3,4,5,7,8,8a-hexahydro-2H-naphthalen-1-yl]methyl acetate
• CAS: 42895-62-5
• 化学式: C₂₄H₃₂O₆
• 分子量: 416.514
• InChiKey: MIHQWPSKQMBDJT-OUHGZSMOSA-N

物化性质

• 沸点：
  519.8±45.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  乙酸酐 、 穿心莲内酯 在 吡啶 作用下， 反应 12.0h， 以46%的产率得到3,19-O-diacetyl-14-deoxy-14,15-didehydroandrographolide
  参考文献：
  名称：

  Specificity and Inhibitory Mechanism of Andrographolide and Its Analogues as Antiasthma Agents on NF-κB p50

  摘要：

  Andrographolide (1) is a diterpenoid lactone with an a,beta-unsaturated lactone group that inhibits NF kappa B DNA binding. Andrographolide reacts with the nucleophilic Cys62 of NF-kappa B p50 through a Michael addition at the Delta(12(13)) exocylic double bond to form a covalent adduct. Using computer docking, site-directed mutagenesis, and mass spectrometry, the noncovalent interactions between andrographolide and additional binding site residues other than Cys62 were found to be essential for the covalent incorporation of andrographolide. Furthermore, the addition reaction of andrographolide on Cys62 was highly dependent on the redox conditions and on the vicinity of nearby, positively charged Arg residues in the conserved RxxRxR motif. The reaction mechanisms of several of the analogues were determined, showing that 14-deoxy-11,12-didehydroandrographolide (8) reacts with NF-kappa B p50 via a novel mechanism distinct from andrographolide. The noncovalent interaction and redox environment of the binding site should be considered, in addition to the electrophilicity, when designing a covalent drug. Analogues similar in structure appear to use distinct reaction mechanisms and may have very different cytotoxicities, e.g., compound 6.

  DOI：

  10.1021/np5007179

文献信息

• Anti-inflammatory Activity of New Compounds from Andrographis paniculata by NF-κB Transactivation Inhibition
  作者：Wen-Wan Chao、Yueh-Hsiung Kuo、Bi-Fong Lin

  DOI：10.1021/jf903629j

  日期：2010.2.24

  inhibitory activity by hydrogenation, oxidation, or acetylation to become four derived compounds, 9, 10, 11, and 12. All of the compounds significantly decreased TNF-α, IL-6, macrophage inflammatory protein-2 (MIP-2), and nitric oxide (NO) secretions from LPS/IFN-γ stimulated RAW 264.7 cells. Compounds 5, 11, and 12 exerted the strongest inhibitory effect on NF-κB-dependent transactivation in the RAW 264

  先前的研究表明穿心莲（AP）的乙酸乙酯（EtOAc）馏分具有抗炎活性。这项研究进一步从生物活性指导的色谱分离中分离了这些活性化合物，并鉴定出八种纯化合物。报告基因检测结果表明，5-羟基-7,8-二甲氧基黄酮（1），5-羟基-7,8-二甲氧基黄酮（2），β-​​谷甾醇（3a）和豆甾醇（3b）的混合物，麦角固醇过氧化物（4），14-脱氧-14,15-脱氢穿心莲内酯（5）和一种新化合物19 - O-乙酰基-14-脱氧-11,12-二脱氢穿心莲内酯（6a）显着抑制LPS /IFN-γ刺激的RAW 264.7巨噬细胞中NF-κB的转录活性（P <0.05）。两种最丰富的化合物，14-脱氧-11,12-二去氢穿心莲内酯（7）和穿心莲内酯（8），具有较少的抑制活性，而且施加更大的抑制活性通过加氢，氧化，或乙酰化，成为4种衍生的化合物，9，10，11和12。所有这些化合物均显着降低了LPS /IFN-γ刺激的RAW
• Synthesis, structure–activity relationships and biological evaluation of dehydroandrographolide and andrographolide derivatives as novel anti-hepatitis B virus agents
  作者：Hao Chen、Yun-Bao Ma、Xiao-Yan Huang、Chang-An Geng、Yong Zhao、Li-Jun Wang、Rui-Hua Guo、Wen-Juan Liang、Xue-Mei Zhang、Ji-Jun Chen

  DOI：10.1016/j.bmcl.2014.03.060

  日期：2014.5

  Dehydroandrographolide and andrographolide, two natural diterpenoids isolated from Andrographis paniculata possessed activity against HBV DNA replication with IC50 values of 22.58 and 54.07 mu M and low SI values of 8.7 and 3.7 in our random assay. Consequently, 48 derivatives of dehydroandrographolide and andrographolide were synthesized and evaluated for their anti-HBV properties to yield a series of active derivatives with lower cytotoxicity, including 14 derivatives against HBsAg secretion, 19 derivatives against HBeAg secretion and 38 derivatives against HBV DNA replication. Interestingly, compound 4e could inhibit not only HBsAg and HBeAg secretions but also HBV DNA replication with SI values of 20.3, 125.0 and 104.9. Furthermore, the most active compound 2c with SI value higher than 165.1 inhibiting HBV DNA replication was revealed with the optimal logP value of 1.78 and logD values. Structureactivity relationships (SARs) of the derivatives were disclosed for guiding the future research toward the discovery of new anti-HBV drugs. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis of andrographolide analogues and their neuroprotection and neurite outgrowth-promoting activities
  作者：Yuanzhen Xu、Hongbo Wei、Jianping Wang、Weiwei Wang、Jinming Gao

  DOI：10.1016/j.bmc.2019.04.025

  日期：2019.6

  Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and remains incurable. Currently, neuronal injury and synapse loss have been considered to be main features in the pathophysiology of AD. Thus, modulation of neuronal survival and neurite outgrowth may represent an efficient strategy for the treatment of AD. Based on the isolates from the traditional medicine Andrographis paniculata, a series of andrographolide analogues were prepared and evaluated for the neuroprotection and neurotrophic activity. Two compounds (3 and 12) could effectively inhibit LPS-induced NO production and iNOS expression as well as proinflammatory cytokines TNF-alpha and IL-6. Moreover, pretreatment with 3 and 12 could protect neurons against microgli-amediated neurotoxicity. Further, H2O2- and 6-OHDA induced neurotoxicity in PC12 cells were also attenuated by the novel 12. Our next study indicated that compounds 1, 4 and 10 promoted NGF-induced neurite outgrowth in PC12 cells, with 10 the most potent. To clarify the underlying mechanisms of active compounds (3, 10 and 12), system pharmacology was employed. The results revealed that muscarinic acetylcholine receptors (mAChRs) may be the main targets of 12 against AD, while thyroid hormone signaling pathway was involved in the mechanisms of 10. These study point to the therapeutic potential of andrographolide analogues against AD.