Synthesis and Evaluations of Novel Apocynin Derivatives as Anti-Glioma Agents

被引：21

作者：

Yang, Tao ^{[1
,2
,3
]}

Zang, Da-Wei ^{[1
,2
]}

Shan, Wei ^{[1
,2
,3
]}

Guo, An-Chen ^{[1
,2
,3
]}

Wu, Jian-Ping ^{[2
,4
]}

Wang, Yong-Jun ^{[1
,2
,3
,4
]}

Wang, Qun ^{[1
,2
,3
]}

机构：

[1] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China

[2] Capital Med Univ, Beijing Tiantan Hosp, China Natl Clin Res Ctr Neurol Dis, Beijing, Peoples R China

[3] Capital Med Univ, Beijing Inst Brain Disorders, Beijing, Peoples R China

[4] Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Beijing, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2019年 / 10卷

基金：

国家重点研发计划;

关键词：

apocynin derivatives; blood-brain barrier; anti-glioma; apoptosis; NF-kappa B activation; BLOOD-BRAIN-BARRIER; NADPH OXIDASES; CANCER; CELL; NOX; INHIBITOR; AUTOPHAGY; STRESS; INJURY; MODEL;

D O I：

10.3389/fphar.2019.00951

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Apocynin (4-hydroxy-3-methoxyacetophenone) is a natural polyphenolic compound with multiple biological activities. In the present study, a series of apocynin derivatives were designed and synthesized. The in silico ADMET prediction, blood-brain barrier (BBB) penetration assay, anti-NADPH oxidase activity, reactive oxygen species (ROS) levels, and anti-glioma effects of these apocynin derivatives were evaluated. The anti-glioma mechanisms of candidate compounds were studied by flow cytometer and Western blot. The results showed that D31 exhibited higher BBB penetration, increased ROS generations and significant anti-glioma effects both in vitro and in vivo. Further studies showed that D31 inhibited the activations of NF-kappa B pathway. Overall, our data demonstrated that D31 inhibited growth and induced apoptosis of glioma, which might be caused by ROS-related NF-kappa B activation. The current study suggested that D31 could be further explored for its potential use in anti-glioma therapy.

引用

页数：15

共 27 条

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