Title:Design, Synthesis, and Evaluation of Isoindoline Derivatives as New Antidepressant
Agents
Volume: 19
Issue: 8
Author(s): Ai-Ling Sun, Chao-Chao Wang, Hao Zhou, Yi-Fei Lang, Shu-Yue Fu, Ren-Min Liu*Kang Lei*
Affiliation:
- School
of Pharmaceutical Sciences, Liaocheng University, Liaocheng, Shandong 252059, China
- School
of Pharmaceutical Sciences, Liaocheng University, Liaocheng, Shandong 252059, China
Keywords:
Isoindoline, synthesis, antidepressant screening, in vivo, molecular docking studies, forced swimming test, tail suspension test.
Abstract:
Background: Isoindoline derivatives exhibit a wide range of biological activities and have
attracted considerable attention. However, few studies have been conducted on their antidepressant activity.
Objective: Here, we designed and synthesized a series of isoindoline derivatives and studied their antidepressant
activities.
Methods: Forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant
activity of the target compounds. The most active compound was used to evaluate the exploratory
activity of the animals by the open-field test. 5-HT concentration was estimated to evaluate if the compound
has an effect on the mice brain by using ELISA. The biological activities of the compounds were
verified by molecular docking studies. The pharmacokinetic properties of the target compounds were
predicted by Discovery Studio (DS) 2020.
Results: The results of the pharmacological experiments showed that most isoindoline derivatives exhibited
significant antidepressant activity. Among these compounds, compound 4j 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 isoindoline derivatives may be mediated by elevated 5-HT levels. Compound 4j
was used in molecular docking experiments to simulate the possible interaction of these compounds with
the 5-HT1A receptor. The results demonstrated that compound 4j had a significant interaction with amino
acids around the active site of the 5-HT1A receptor in the homology model.
Conclusion: Isoindoline derivatives synthesized in this study have a significant antidepressant activity.
These findings can be useful in the design and synthesis of novel antidepressants.