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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00951

Synthesis and evaluations of novel apocynin derivatives as anti-glioma agents

Tao Yang1, Da-Wei Zang1, Wei Shan1, An-Chen Guo1,  Jian-Ping Wu2,  Yong-Jun Wang1 and  Qun Wang1*
  • 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China
  • 2National Center for Clinical Medicine of Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, China

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-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.

Keywords: Apocynin derivatives,, Blood-Brain Barrier, Anti-glioma, Apoptosis, NF-κB activation

Received: 20 May 2019; Accepted: 25 Jul 2019.

Copyright: © 2019 Yang, Zang, Shan, Guo, Wu, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Qun Wang, Beijing Tiantan Hospital, Capital Medical University, Department of Neurology, Beijing, 100050, China, wangq@ccmu.edu.cn