Frontiers in Pharmacology (Jun 2022)
The Anti-Glioma Effect of Juglone Derivatives through ROS Generation
- Jinsen Zhang,
- Jinsen Zhang,
- Jinsen Zhang,
- Jinsen Zhang,
- Jinsen Zhang,
- Minjie Fu,
- Minjie Fu,
- Minjie Fu,
- Minjie Fu,
- Minjie Fu,
- Jinfeng Wu,
- Fengfeng Fan,
- Fengfeng Fan,
- Fengfeng Fan,
- Fengfeng Fan,
- Fengfeng Fan,
- Xin Zhang,
- Xin Zhang,
- Xin Zhang,
- Xin Zhang,
- Xin Zhang,
- Chunjie Li,
- Hui Yang,
- Hui Yang,
- Hui Yang,
- Hui Yang,
- Hui Yang,
- Yonghe Wu,
- Yiming Yin,
- Wei Hua,
- Wei Hua,
- Wei Hua,
- Wei Hua,
- Wei Hua
Affiliations
- Jinsen Zhang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Jinsen Zhang
- National Center for Neurological Disorders, Shanghai, China
- Jinsen Zhang
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Jinsen Zhang
- Neurosurgical Institute of Fudan University, Shanghai, China
- Jinsen Zhang
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Minjie Fu
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Minjie Fu
- National Center for Neurological Disorders, Shanghai, China
- Minjie Fu
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Minjie Fu
- Neurosurgical Institute of Fudan University, Shanghai, China
- Minjie Fu
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Jinfeng Wu
- Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
- Fengfeng Fan
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Fengfeng Fan
- National Center for Neurological Disorders, Shanghai, China
- Fengfeng Fan
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Fengfeng Fan
- Neurosurgical Institute of Fudan University, Shanghai, China
- Fengfeng Fan
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Xin Zhang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Xin Zhang
- National Center for Neurological Disorders, Shanghai, China
- Xin Zhang
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Xin Zhang
- Neurosurgical Institute of Fudan University, Shanghai, China
- Xin Zhang
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Chunjie Li
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Hui Yang
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Hui Yang
- National Center for Neurological Disorders, Shanghai, China
- Hui Yang
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Hui Yang
- Neurosurgical Institute of Fudan University, Shanghai, China
- Hui Yang
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- Yonghe Wu
- Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China
- Yiming Yin
- Departmeng of Neurosurgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
- Wei Hua
- Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China
- Wei Hua
- National Center for Neurological Disorders, Shanghai, China
- Wei Hua
- Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China
- Wei Hua
- Neurosurgical Institute of Fudan University, Shanghai, China
- Wei Hua
- Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
- DOI
- https://doi.org/10.3389/fphar.2022.911760
- Journal volume & issue
-
Vol. 13
Abstract
Juglone has been extensively reported as a natural antitumor pigment. However, it is easy to be oxidized due to active hydroxy in the quinone. Here, we designed some new juglone derivatives, as the hydroxy was replaced by methyl (D1), allyl (D2), butyl (D3), and benzyl (D4) groups. Nuclear magnetic resonance spectra and mass spectrometry were applied to confirm the derivatives and oxidative products of juglone. U87 and U251 cell lines were used for tests in vitro, and primary human glioblastoma cells were applied for in vivo experiments. The CCK8 and EdU assay demonstrated the anti-tumor effect of the four derivatives, and IC50 for U87 was 3.99, 3.28, 7.60, and 11.84 μM, respectively. In U251, IC50 was 7.00, 5.43, 8.64, and 18.05 μM, respectively. D2 and D3 were further selected, and flow cytometry showed that apoptosis rates were increased after D2 or D3 treatment via ROS generation. Potential targets were predicted by network pharmacology analysis, most of which were associated with apoptosis, cell cycle, and metabolism pathway. CDC25B and DUSP1 were two of the most likely candidates for targets. The orthotopic glioblastoma model was established to evaluate the anti-glioma effect and side-effect of juglone derivatives, and the in vivo experiments confirmed the anti-glioma effects of juglone derivatives. In conclusion, new derivatives of juglone were created via chemical group substitution and could inhibit glioma cell viability and proliferation and induce apoptosis rate via ROS generation.
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