Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H3 Agents: Synthesis and Biological Evaluation

In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound <b>11b</b> demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H<sub>3</sub> receptor (H<sub>3</sub>R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound <b>11b</b> when it forms a complex with SERT, NET, and the histamine H<sub>3</sub> receptor. In vivo behavioral studies, compound <b>11b</b> dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound <b>11b</b> had a favorable pharmacokinetic profile in rats. Thus, compound <b>11b</b> has the potential to develop a novel class of drugs for the treatment of depression.

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Journal
Molecules
Published
2024-11-06
DOI
https://doi.org/10.3390/molecules29225240
Primary Topic
Computational Drug Discovery Methods
Type
article
Field-Weighted Citation Impact
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article

Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H3 Agents: Synthesis and Biological Evaluation

Quxiang Li, Yufan Qiu, Cuimei Xu, Guoguang Chen et al.
Molecules
Computational Drug Discovery Methods
article

Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H3 Agents: Synthesis and Biological Evaluation

Quxiang Li, Yufan Qiu, Cuimei Xu, Guoguang Chen, Xiangqing Xu, Dongli Wang, Lili Ren, Jian Feng, Junyong Luo
article en

Abstract

In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound <b>11b</b> demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H<sub>3</sub> receptor (H<sub>3</sub>R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound <b>11b</b> when it forms a complex with SERT, NET, and the histamine H<sub>3</sub> receptor. In vivo behavioral studies, compound <b>11b</b> dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound <b>11b</b> had a favorable pharmacokinetic profile in rats. Thus, compound <b>11b</b> has the potential to develop a novel class of drugs for the treatment of depression.

MoleculesVol. 29(22)
Nanjing Tech University (CN), Jiangsu Nhwa Pharmaceutical (China) (CN)
Pharmaron, National Science and Technology Major Project
Good health and well-being
Openalex Percentile: Top 76%
Computational Drug Discovery Methods
DOIOpen Access PDFOpenAlex
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Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H3 Agents: Synthesis and Biological Evaluation — Quxiang Li, Yufan Qiu, et al. · Molecules (2024) | TGRS Research Map | TGRS