7-(phenylcarbamate)cadalene

• 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: 7-(phenylcarbamate)cadalene
• 英文别名: 7-(phenylcarbamate)-3,4-dihydrocadalene；(3,8-dimethyl-5-propan-2-ylnaphthalen-2-yl) N-phenylcarbamate
• 化学式: C₂₂H₂₃NO₂
• 分子量: 333.43
• InChiKey: FXVKNXSTSPOTHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (-)-(4R)-7-hydroxy-3,4-dihydrocadalene 、 异氰酸苯酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以79%的产率得到7-(phenylcarbamate)cadalene
  参考文献：
  名称：

  Effect of natural and semi-synthetic cadinanes from Heterotheca inuloides on NF-κB, Nrf2 and STAT3 signaling pathways and evaluation of their in vitro cytotoxicity in human cancer cell lines

  摘要：

  The effects of ten natural cadinane sesquiterpenoids isolated from Heterotheca inuloides on the pathways of the NF-kappa B, Nrf2 and STAT3 transcription factors were studied for the first time. The main constituent in this species, 7-hydroxy-3,4-dihydrocadalene (1), showed anti-NE-kappa B activity and activated the antioxidant Nrf2 pathway, which may explain the properties reported for the traditional use of the plant. In addition to the main metabolite, a structurally similar compound, 7-hydroxy-cadalene (2), also displayed anti-NE-kappa B activity. Thus, both natural compounds were used as templates for the preparation of a novel semi-synthetic derivative set, including esters and carbamates, which were evaluated for their potential in vitro antiproliferative activities against six human cancer cell lines. Carbamate derivatives 32 and 33 were found to exhibit potent activity against human colorectal adenocarcinoma and showed important selectivity in cancer cells. Among ester derivatives, compound 13 was determined to be a more potent NE-kappa B inhibitor and Nrf2 activator than its parent, 7-hydroxy-3,4-dihydrocadalene (1). Furthermore, this compound decreases levels of phospho-IKBa, a protein complex involved in the NE-kappa B activation pathway. Molecular simulations suggest that all active compounds interact with the activation loop of the IKKI3 subunit in the IKK complex, which is the responsible of IKBoc phosphorylation. Thus, we identified two natural, and one semi-synthetic, NF-kappa B and Nrf2 modulators and two new promising cytotoxic compounds. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.03.069

文献信息

• Effect of natural and semi-synthetic cadinanes from Heterotheca inuloides on NF-κB, Nrf2 and STAT3 signaling pathways and evaluation of their in vitro cytotoxicity in human cancer cell lines
  作者：Verónica Egas、Estrella Millán、Juan A. Collado、Teresa Ramírez-Apan、Carlos A. Méndez-Cuesta、Eduardo Muñoz、Guillermo Delgado

  DOI：10.1016/j.bmc.2017.03.069

  日期：2017.6

  The effects of ten natural cadinane sesquiterpenoids isolated from Heterotheca inuloides on the pathways of the NF-kappa B, Nrf2 and STAT3 transcription factors were studied for the first time. The main constituent in this species, 7-hydroxy-3,4-dihydrocadalene (1), showed anti-NE-kappa B activity and activated the antioxidant Nrf2 pathway, which may explain the properties reported for the traditional use of the plant. In addition to the main metabolite, a structurally similar compound, 7-hydroxy-cadalene (2), also displayed anti-NE-kappa B activity. Thus, both natural compounds were used as templates for the preparation of a novel semi-synthetic derivative set, including esters and carbamates, which were evaluated for their potential in vitro antiproliferative activities against six human cancer cell lines. Carbamate derivatives 32 and 33 were found to exhibit potent activity against human colorectal adenocarcinoma and showed important selectivity in cancer cells. Among ester derivatives, compound 13 was determined to be a more potent NE-kappa B inhibitor and Nrf2 activator than its parent, 7-hydroxy-3,4-dihydrocadalene (1). Furthermore, this compound decreases levels of phospho-IKBa, a protein complex involved in the NE-kappa B activation pathway. Molecular simulations suggest that all active compounds interact with the activation loop of the IKKI3 subunit in the IKK complex, which is the responsible of IKBoc phosphorylation. Thus, we identified two natural, and one semi-synthetic, NF-kappa B and Nrf2 modulators and two new promising cytotoxic compounds. (C) 2017 Elsevier Ltd. All rights reserved.