andrographolic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: andrographolic acid
• 英文别名: (E)-4-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]-2-[(1S)-1,2-dihydroxyethyl]but-2-enoic acid
• 化学式: C₂₀H₃₂O₆
• 分子量: 368.47
• InChiKey: CBJRVSWMDLZAQD-OTESTREVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  118
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  穿心莲内酯 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以75%的产率得到andrographolic acid
  参考文献：
  名称：

  合成与穿心莲内酯衍生物作为有效的抗骨质疏松症药物的评价在体外和体内

  摘要：

  在这项工作中，我们发现穿心莲内酯的衍生物（AP，1）14-脱氧-11,12-二氢加氢穿心莲内酯（2）与AP相比具有大大降低的细胞毒性，并表现出中等的抗破骨细胞生成活性。通过在2的C-19处引入抗骨质疏松症的化学型，合成了30种化合物。他们中的六个表现出比AP更强的破骨细胞抑制作用。值得注意的是，化合物12g表现出最强的活性，IC 50值为0.35μM。通过12g处理，破骨细胞特异性基因（例如TRAcP，CTSK，NFATc1和MMP-9）的表达水平也降低了。此外，蛋白质印迹和免疫荧光分析表明该化合物12g通过下调RANKL诱导的NF-κB信号通路抑制破骨细胞分化。在卵巢切除（OVX）雌性小鼠模型中，化合物12g显着改善了骨质流失。因此，化合物12g显示出有希望的体内功效和低毒性，表明其治疗骨质疏松症的治疗潜力。

  DOI：

  10.1016/j.ejmech.2021.113185

文献信息

• 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.