Frontiers in Pharmacology (Sep 2019)

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

  • Tao Yang,
  • Tao Yang,
  • Tao Yang,
  • Da-Wei Zang,
  • Da-Wei Zang,
  • Wei Shan,
  • Wei Shan,
  • Wei Shan,
  • An-Chen Guo,
  • An-Chen Guo,
  • An-Chen Guo,
  • Jian-Ping Wu,
  • Jian-Ping Wu,
  • Yong-Jun Wang,
  • Yong-Jun Wang,
  • Yong-Jun Wang,
  • Yong-Jun Wang,
  • Qun Wang,
  • Qun Wang,
  • Qun Wang

DOI
https://doi.org/10.3389/fphar.2019.00951
Journal volume & issue
Vol. 10

Abstract

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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.

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