烷基酚类死亡相关凋亡诱导蛋白激酶2 (DRAK2)小分子抑制剂的设计与合成研究
收稿日期: 2021-03-29
修回日期: 2021-04-29
网络出版日期: 2021-05-14
Design and Synthesis of Alkyl Phenols Inhibitors of Death Associated Apoptotic Protein Kinase 2 (DRAK2)
Received date: 2021-03-29
Revised date: 2021-04-29
Online published: 2021-05-14
死亡相关凋亡诱导蛋白激酶2 (DRAK2)为苏氨酸/丝氨酸激酶, 是死亡相关蛋白激酶(DAPK)家族中的一员, 在外界刺激的作用下, 其过表达具有诱导细胞凋亡的能力. 已知高糖、高脂和某些细胞炎性因子均可诱导DRAK2的高表达而引起胰岛β细胞凋亡, 提示DRAK2可能在其中扮演着重要的介导作用, 因此靶向DRAK2的小分子抑制剂可能为糖尿病治疗提供了一种很有前景的方案. 本工作通过对烷基酚类化合物8a进行结构改造, 得到了约30个活性化合物, 并初步确定了此类新型DRAK2抑制剂的构效关系.
关键词： 死亡相关凋亡诱导蛋白激酶2; 糖尿病; 烷基酚类; 抑制剂
张正 , 戴成球 , 吴红红 , 李静雅 , 南发俊 . 烷基酚类死亡相关凋亡诱导蛋白激酶2 (DRAK2)小分子抑制剂的设计与合成研究[J]. 有机化学, 2021 , 41(8) : 3204 -3213 . DOI: 10.6023/cjoc202103056
Death associated apoptotic protein kinase 2 (DRAK2) is a threonine/serine kinase and a member of the death- associated protein kinase (DAPK) family. Under the action of external stimuli, its overexpression has the ability to induce apoptosis. High glucose, high fat, and certain cellular inflammatory factors can induce the high expression of DRAK2, thereby causing pancreatic β-cell apoptosis. DRAK2 may play a mediating role in the process. Therefore, small molecule inhibitors targeting DRAK2 own good development prospects to treat diabetes. In this work, more than 20 active compounds were obtained through structural modification of the alkylphenols compound 8a, and the structure-activity relationship between them was preliminarily determined.
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