Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants

doi:10.1007/s00044-022-02973-0

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	Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants
	Li, Tian-Ze; Huang, Xiao-Yan; Sun, Jin-Jin; Geng, Chang-An; Zhang, Xue-Mei; Chen, Ji-Jun
	2022
发表期刊	MEDICINAL CHEMISTRY RESEARCH
卷号	31 期号:11 页码:2045-2057
摘要	The antidepressant activity of (+) and (-)-paeoveitol was first evaluated using the forced swimming test (FST), and (+)-paeoveitol showed potential antidepressant activity by decreasing immobility time of mice (by approximately 26.4%) in the FST at a dose of 20 mg/kg. To explore the structure-activity relationships (SARs) and obtain more potent compounds, twenty derivatives of (+)-paeoveitol were synthesized and evaluated for their agonistic activities on melatonin type I (MT1) and type II (MT2) receptors. As a results, compound 13 with an N-methylpiperazine fragment exhibited obvious effect on MT1 and MT2 receptors with EC50 values of 0.20 and 0.24 mM. Moreover, compound 13 dose-dependently decreased the immobility of mice in the FST and showed an inverted U-shaped dose-effect, and the most efficacious dose (at 40 mg/kg) was comparable to fluoxetine (20 mg/kg) with a reduced immobility time of 29.2% and 34.5%, respectively. In vivo neurochemical assays suggested that compound 13 obviously increased 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) levels in the mice brain, indicating that its antidepressant effects might be related to the monoaminergic system. In silico ADMET study revealed that 13 has favorable pharmacokinetic properties. These findings suggest that compound 13 could be a potential antidepressant agent. [GRAPHICS] .
关键词	(+)-Paeoveitol derivatives Antidepressant Forced swimming test Monoamine neurotransmitter
DOI	10.1007/s00044-022-02973-0
收录类别	SCI
WOS记录号	WOS:000855589000002
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74644
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Li, Tian-Ze,Huang, Xiao-Yan,Sun, Jin-Jin,et al. Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants[J]. MEDICINAL CHEMISTRY RESEARCH,2022,31(11):2045-2057.
APA	Li, Tian-Ze,Huang, Xiao-Yan,Sun, Jin-Jin,Geng, Chang-An,Zhang, Xue-Mei,&Chen, Ji-Jun.(2022).Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants.MEDICINAL CHEMISTRY RESEARCH,31(11),2045-2057.
MLA	Li, Tian-Ze,et al."Synthesis and biological evaluation of (+)-paeoveitol derivatives as novel antidepressants".MEDICINAL CHEMISTRY RESEARCH 31.11(2022):2045-2057.

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