Abstract
In this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim test (FST) and the tail suspension test (TST), were used to determine the antidepressant activity of coumarin derivatives. Compounds that showed potential activity were analyzed for their effects on 5-hydroxytryptamine (5-HT) levels in the brains of mice. Molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT1A receptor was also be predicted. The results of the pharmacological experiments showed that most coumarin derivatives exhibited significant antidepressant activity. Among these compounds, 7-(2-(4-(4-fluorobenzyl)piperazin-1-yl)-2-oxoethoxy)-2H-chromen-2-one (6i) showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels. The results of molecular docking demonstrated that compound 6i had a significant interaction with amino acids around the active site of the 5-HT1A receptor in the homology model. The physicochemical and pharmacokinetic properties of the target compounds were also predicted using Discovery Studio (DS) 2020 and Chemdraw 14.0.
Highlights
Many neurotransmitter systems are known to cause CNS diseases [1,2,3]
The results of the measurements of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels
The newly synthesized target compounds were characterized by the high-resolution mass spectrometry (HRMS), 1 H, and
Summary
Many neurotransmitter systems are known to cause CNS diseases [1,2,3]. One of the common dysfunctions of the CNS is depression, whose occurrence is connected with disturbances in the functions of the serotonin and dopamine systems. Drug therapy is the main method of depression treatment. These drugs mainly increase the concentration of serotonin, norepinephrine, or dopamine at the synapse by inhibiting membrane transporters or blocking the degradation of these neurotransmitters by monoamine oxidase. These drugs have certain adverse reactions and low efficacy [4,5]. The development of novel antidepressants with high efficiency and low toxicity is an effective strategy for the treatment of depression
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