| Autor: |
Xueyang Xiao, Zhou Tong, Yuexing Zhang, Hui Zhou, Mengying Luo, Tianhui Hu, Ping Hu, Luqi Kong, Zeqin Liu, Chan Yu, Zhiyong Huang, Linzhen Hu |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Marine Drugs, Vol 20, Iss 3, p 191 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1660-3397 |
| DOI: |
10.3390/md20030191 |
| Popis: |
Oxidative stress has been implicated in the etiology of Parkinson’s disease (PD). Molecules non-covalently binding to the Keap1–Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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