Synthesis and biological evaluation of clovamide analogues with catechol functionality as potent Parkinson's disease agents in vitro and in vivo
Synthesis and biological evaluation of clovamide analogues with catechol functionality as potent Parkinson's disease agents in vitro and in vivo
复制标题
具有儿茶酚功能的克洛酰胺类似物作为有效的帕金森病药物的体外和体内的合成和生物学评价
DOI：
10.1016/j.bmcl.2018.11.030
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发表时间：
2019-01-15
影响因子：
2.7
通讯作者：
Wang, Hao
中科院分区：
文献类型：
--
作者：
Feng, Jia-Hao;Hu, Xiao-Long;Wang, Hao
In this study, seven clovamide analogues (1-7) were designed and synthesized, and the neuroprotection of 1-7 as well as 8-15 (prepared in our previous work) against H2O2-induced oxidative stress was evaluated in SH-SY5Y cells. Results showed that 1-7 with catechol groups exhibited better neuroprotective effects than 8-15, and their EC50 values ranged from 4.26 to 23.83 mu M, especially 1, indicating that the moiety of catechol governed the activities of these compounds. Furthermore, oral administration of 1 (10 or 20 mg/kg) was demonstrated to possess anti-PD effect through alleviating apoptosis and oxidative stress in vitro and in vivo, and to up-regulate the expression of heme oxygenase-1 (HO-1) via PI3K/AKT/mTOR pathway. Finally, the pharmacokinetic (PK) assessment of 1 was determined in rats. These findings suggested that 1 might be an effective candidate for PD therapy.
