A Computational Investigation of Potential 5-HT 2C Receptor Inhibitors for Treating Schizophrenia by ADMET Profile Analysis, Molecular Docking, DFT, Network Pharmacology, and Molecular Dynamic Simulation

Background: Schizophrenia manifests through behavioral abnormalities, suicidal ideation, and neuropsychological deficits. Hence, this study focused on 5-hydroxytryptamine (5-HT 2C) which influenced the modulation of the series of events that lead to schizophrenia. Methodology: Based on the computati...

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Bibliographic Details
Main Authors: Mohammed Raihan Uddin, Mahira Rahman, Mosammad Jannatun Nayem Rafin, Joya Datta Ripa
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Chemistry Proceedings
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Online Access:https://www.mdpi.com/2673-4583/16/1/69
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Summary:Background: Schizophrenia manifests through behavioral abnormalities, suicidal ideation, and neuropsychological deficits. Hence, this study focused on 5-hydroxytryptamine (5-HT 2C) which influenced the modulation of the series of events that lead to schizophrenia. Methodology: Based on the computational study, the potential 5-HT 2C inhibitors such as Ephemeranthoquinone from <i>Arundina graminifolia</i> and Actinodaphnine from <i>Litsea polyantha</i> were determined. The candidate ligands were optimized using the Gaussian 16 software package and the DFT 6-31g (d,p) basis set. The interaction between the ligands and proteins was examined with PyRx 0.8. Additionally, pharmacokinetics was assessed using SwissADME, and Protox II for toxicity prediction. The network pharmacology study was examined by using the STRING database and the Cytoscape 3.10.1 tool. Moreover, a 100-nanosecond molecular dynamics simulation analysis using Desmond to ensure the stability of these two compounds was carried out. Result: This computational research observed that ephemeranthoquinone and actinodaphnine are the most selective 5-HT 2C inhibitors due to their docking score, optimization, and molecular dynamics simulation results. Conclusions: These compounds are required to be studied further to develop a useful 5-HT 2C inhibitors for the treatment of schizophrenia.
ISSN:2673-4583