Yang Tao, Zang Da-Wei, Shan Wei, Guo An-Chen, Wu Jian-Ping, Wang Yong-Jun, Wang Qun
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Centre for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Front Pharmacol. 2019 Sep 3;10:951. doi: 10.3389/fphar.2019.00951. eCollection 2019.
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 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 and . Further studies showed that D31 inhibited the activations of NF-κB pathway. Overall, our data demonstrated that D31 inhibited growth and induced apoptosis of glioma, which might be caused by ROS-related NF-κB activation. The current study suggested that D31 could be further explored for its potential use in anti-glioma therapy.
白杨素（4-羟基-3-甲氧基苯乙酮）是一种具有多种生物活性的天然多酚化合物。在本研究中，设计并合成了一系列白杨素衍生物。评估了这些白杨素衍生物的药物代谢动力学（ADMET）预测、血脑屏障（BBB）通透性测定、抗NADPH氧化酶活性、活性氧（ROS）水平以及抗胶质瘤作用。通过流式细胞仪和蛋白质免疫印迹法研究了候选化合物的抗胶质瘤机制。结果表明，D31表现出更高的血脑屏障通透性、增加的ROS生成以及显著的体内外抗胶质瘤作用。进一步研究表明，D31抑制了NF-κB通路的激活。总体而言，我们的数据表明，D31抑制胶质瘤生长并诱导其凋亡，这可能是由ROS相关的NF-κB激活引起的。目前的研究表明，D31在抗胶质瘤治疗中的潜在用途值得进一步探索。
