中南大学
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返回首页Efficient Synthesis of Icetexane Diterpenes and Apoptosis Inducing Effect by Upregulating BiP-ATF4-CHOP Axis in Colorectal Cells
发布时间：2021-06-29
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- DOI码：
- 10.1021/acs.jnatprod.1c00310
- 所属单位：
- 中南大学湘雅药学院
- 教研室：
- 药物化学系
- 发表刊物：
- Journal of Natural Products
- 刊物所在地：
- USA
- 摘要：
- We herein present an efficient and robust synthetic strategy toward 12 icetexane diterpenes and their derivatives, which features a PPh3/DIAD-mediated rearrangement of the reduced carnosic acid derivative (2) to give (−)-barbatusol (3) in a regioselective and scalable way. MTT assay led to the identification of (+)-grandione (11) and (−)-demethylsalvicanol o-quinone derivative (9) as highly cytotoxic agents against HCT-116, COLO-205, and Caco-2 cells. Interestingly, (+)-grandione (11) induced the HCT-116 cell apoptosis in a dose-dependent manner, which might be attributed to the upregulation of the BiP-ATF4-CHOP axis and promotion of the BiP-ATF4 interactions, thereby leading to endoplasmic reticulum (ER) stress. This work not only paves an efficient and scalable pathway to access icetexane diterpenes but also provides new leads for the development of anticolorectal agents with a unique mode of action.
- 论文类型：
- 文章
- 学科门类：
- 医学
- 一级学科：
- 药学
- 文献类型：
- J
- 是否译文：
- 否
- 发表时间：
- 2021-06-25
- 收录刊物：
- SCI