geopyxin A | 1355610-69-3

• 英文名称: geopyxin A
• 英文别名: (1S,7S)-1,7-dihydroxy-15-oxo-ent-kaur-16-en-19-oic acid；(1R,2S,4S,5R,8S,9S,10S,13R)-2,8-dihydroxy-5,9-dimethyl-14-methylidene-15-oxotetracyclo[11.2.1.01,10.04,9]hexadecane-5-carboxylic acid
• CAS: 1355610-69-3
• 化学式: C₂₀H₂₈O₅
• 分子量: 348.439
• InChiKey: LRECIABFFPIQSO-BALPIQRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  geopyxin A 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以99%的产率得到16,17-dihydogeopyxin A
  参考文献：
  名称：

  Non-covalent NRF2 Activation Confers Greater Cellular Protection than Covalent Activation

  摘要：

  The transcription factor NRF2 confers cellular protection by maintaining cellular redox homeostasis and proteostasis. Basal NRF2 levels are normally low due to KEAP1-mediated ubiquitylation and subsequent proteasomal degradation. KEAP1, a substrate adaptor protein of a KEAP1-CUL3-RBX1 E3 ubiquitin ligase complex, contains a critical cysteine (C151) that is modified by electrophiles or oxidants, resulting in inactivation of the E3 ligase and inhibition of NRF2 degradation. Currently, nearly all NRF2 inducers are electrophilic molecules that possess unwanted off-target effects due to their reactive nature. Here, we report a group of NRF2 inducers, ent-kaurane diterpenoid geopyxins, with and without C151 reactive electrophilic moieties. Among 16 geopyxins, geopyxin F, a non-electrophilic NRF2 activator, showed enhanced cellular protection relative to an electrophilic NRF2 activator, geopyxin C. To our knowledge, this is the first detailed structure-activity relationship study of covalent versus non-covalent NRF2 activators, showing the promise of non-covalent NRF2 activators as potential therapeutic compounds.

  DOI：

  10.1016/j.chembiol.2019.07.011

文献信息

• Geopyxins A–E, <i>ent</i>-Kaurane Diterpenoids from Endolichenic Fungal Strains <i>Geopyxis</i> aff. <i>majalis</i> and <i>Geopyxis</i> sp. AZ0066: Structure–Activity Relationships of Geopyxins and Their Analogues
  作者：E. M. Kithsiri Wijeratne、Bharat P. Bashyal、Manping X. Liu、Danilo D. Rocha、G. M. Kamal B. Gunaherath、Jana M. U’Ren、Malkanthi K. Gunatilaka、A. Elizabeth Arnold、Luke Whitesell、A. A. Leslie Gunatilaka

  DOI：10.1021/np200769q

  日期：2012.3.23

  Four new ent-kaurane diterpenoids, geopyxins A–D (1–4), were isolated from Geopyxis aff. majalis, a fungus occurring in the lichen Pseudevernia intensa, whereas Geopyxis sp. AZ0066 inhabiting the same host afforded two new ent-kaurane diterpenoids, geopyxins E and F (5 and 6), together with 1 and 3. The structures of 1–6 were established on the basis of their spectroscopic data, while the absolute

  四个新的ENT -kaurane二萜类化合物，geopyxins A-d（1 - 4）中，从分离Geopyxis AFF。majalis，一种发生在Pseudevernia iNTensa地衣中的真菌，而Geopyxis sp。AZ0066 栖息在同一宿主中，提供了两种新的eNT - kaurane 二萜，geopyxins E 和 F（5和6），以及1和3。1 – 6的结构是基于它们的光谱数据建立的，而绝对构型是使用改进的 Mosher 酯方法分配的。甲基化1 – 3、5和6给出了它们相应的甲酯7 – 11。乙酰化后，1和7产生了它们相应的单乙酸酯12和14以及二乙酸酯13和15。评估所有化合物的细胞毒性和热休克诱导活性。化合物2，7 - 10，12，14，和15显示出对所测试的所有五个癌细胞系低微摩尔范围的细胞毒活性，但只有化合物7 - 9，14，和15被发现在激活相似浓度的热休克响应