自噬
神经保护
PI3K/AKT/mTOR通路
蛋白激酶B
化学
区域选择性
对接(动物)
药理学
生物化学
立体化学
信号转导
生物
医学
细胞凋亡
催化作用
护理部
作者
Jie Li,Fan Yang,Linwei Zeng,Fangmin Zhang,Chang‐Xin Zhou,Li‐She Gan
标识
DOI:10.1021/acs.jnatprod.0c00830
摘要
6-Formylisoophiopogonone B (7a) and 8-formylophiopogonone B (7b), two natural products isolated from Ophiopogon japonicus, represent a subgroup of rare 6/8-formyl/methyl-homoisoflavonoid skeletons. Herein we report an efficient method for the synthesis of these formyl/methyl-homoisoflavonoids. The synthesized compounds were evaluated for their neuroprotective effects on the MPP+-induced SH-SY5Y cell injury model and showed marked activity. Exploration of the neuroprotective mechanisms of compound 7b led to an increased expression of autophagy marker LC3-II and down-regulation of autophagy substrate p62/SQSTM1. Molecular docking studies showed that 7b may prevent the inhibition of the classic PI3K-AKT-mTOR signaling pathway by interfering with the human HSP90AA1.
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