Design, synthesis, and biological evaluation of piperazine derivatives involved in the 5-HT1AR/BDNF/PKA pathway

被引：3
|
作者：
Zhou, Hao [1 ]
Li, Mengjiao [1 ]
Liu, Hui [2 ]
Liu, Zheng [3 ]
Wang, Xuekun [1 ]
Wang, Shiben [1 ]
机构：
[1] Liaocheng Univ, Sch Pharmaceut Sci, 1 Hunan Rd, Liaocheng 252059, Shandong, Peoples R China
[2] Yanbian Univ, Coll Pharm, Yanji 133002, Jilin, Peoples R China
[3] Foshan Univ, Sch Med, Foshan, Guangdong, Peoples R China
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2024年 / 39卷 / 01期
关键词：
Piperazine; antidepressant; western blot; 5-HT1AR; molecular docking studies; UNPREDICTABLE MILD STRESS; ANTIDEPRESSANT ACTIVITY; ARYLPIPERAZINE DERIVATIVES; DYNAMICS;
D O I：
10.1080/14756366.2023.2286183
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In this study, four series of piperazine derivatives were designed, synthesised and subjected to biological test, and compound 6a with potential antidepressant activity was obtained. An affinity assay of compound 6a with 5-hydroxytryptamine (serotonin, 5-HT)(1A) receptor (5-HT1AR) was undertaken, and the effects on the 5-HT level in the brains of mice were also tested. The results showed that compound 6a had the best affinity with 5-HT1AR (K-i = 1.28 nM) and significantly increased the 5-HT level. The expression levels of 5-HT1AR, BDNF, and PKA in the hippocampus were analysed by western blot and immunohistochemistry analyses. The results showed that the expression of 5-HT1AR, BDNF, and PKA in the model group was reduced compared to that of the control group, and compound 6a could reverse this phenomenon. Molecular docking was performed to investigate the interactions of the studied compound 6a with 5-HT1AR on the molecular level. [Graphical Abstract]
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页数：17
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