Target-specific therapeutic assessment of repurposed drug candidates for oral lichen planus: a network pharmacology-molecular dynamics simulation guided investigation

针对口腔扁平苔藓的靶向治疗评估:基于网络药理学-分子动力学模拟指导的研究

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Abstract

BACKGROUND: Oral lichen planus (OLP) is a chronic mucocutaneous autoimmune skin disease without a proper pathophysiology and approved therapy. As a result, several repurposed drugs have been used in clinical practice, and it remains unclear which one holds greater potential. AIM: The present study employs a network pharmacology to explore the disease biology and further investigate the target-specific binding efficacy of repurposed drugs. MATERIALS AND METHODS: Twenty-eight repurposed drug's (D1-D28) efficacies against twelve targets were investigated using PyRx 0.8-AutoDock 4.2 software. Further, drug stability and reactivity were studied using molecular dynamics (MD) simulation at 200 ns, Gibbs free energy, frontier molecular orbital theory, and structural activity relationship. RESULTS: The above computational investigation suggested betamethasone (D2/BETA) and triamcinolone acetonide (D28/TACA) are two potential drugs, predominantly demonstrating higher binding efficacy against the glucocorticoid receptor (GR). Further, MD simulation, free-energy calculation revealed that D28/TACA was comparatively more stable than D2/BETA. CONCLUSION: The network pharmacology explored possible drug targets for drug discovery and showed that D28/TACA is a more effective treatment option among repurposed drugs.

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