Frontiers in bioinformatics · 2026
Sesamum indicum-derived valdiate as a novel neuroprotective agent targeting PDE10A2 and SIRT1 in Huntington's disease.
СтатьяНазвание и аннотация: Перевод в очереди
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Shyam Mukul, Ismail M D Wafi, Sharma Deepak, Srirangan Prathap, Muniyan Rajiniraja, Prince Sabina Evan
Аннотация
BACKGROUND: Huntington's disease is prevalent globally, with approximately 4.88 cases per 100,000 people, based on a systematic review and meta-analysis of 33 studies published between 2010 and 2022. Despite its significant prevalence, no proper treatment is available that directly addresses Huntington's disease. The existing treatments focus on symptom management, such as controlling chorea and psychiatric symptoms. The drugs used for this purpose may also cause side effects, including depression and Parkinson's disease.
METHODS: An integrated experimental and computational approach was employed, involving cold maceration extraction of Sesamum indicum, LC-MS/MS based phytochemical profiling, ADMET screening, molecular docking, molecular dynamics simulations, and MMBPSA binding free energy analysis to identify potential inhibitors of Huntington's diseases associated targets.
RESULTS: Among the LC-MS/MS identified compounds, eight compounds satisfied the ADMET criteria. Valdiate (PubChem CID: 129715809) demonstrated favourable multi-target binding with docking score of -7.3 kcal/mol against HDAC4 and -8.9 kcal/mol against HDAC7. Molecular dynamics simulations confirmed stable protein-ligand interactions, while MMPBSA analysis yielded binding free energies of -23.22 ± 2.45 kcal/mol (HDAC4) and -28.27 ± 2.28 kcal/mol (HDAC7), identifying Valdiate as the most promising potential inhibitor.
CONCLUSION: Valdiate may serve as a potential inhibitor of mutant huntingtin-associated pathological pathways, pending further in-vitro and in-vivo validation.
METHODS: An integrated experimental and computational approach was employed, involving cold maceration extraction of Sesamum indicum, LC-MS/MS based phytochemical profiling, ADMET screening, molecular docking, molecular dynamics simulations, and MMBPSA binding free energy analysis to identify potential inhibitors of Huntington's diseases associated targets.
RESULTS: Among the LC-MS/MS identified compounds, eight compounds satisfied the ADMET criteria. Valdiate (PubChem CID: 129715809) demonstrated favourable multi-target binding with docking score of -7.3 kcal/mol against HDAC4 and -8.9 kcal/mol against HDAC7. Molecular dynamics simulations confirmed stable protein-ligand interactions, while MMPBSA analysis yielded binding free energies of -23.22 ± 2.45 kcal/mol (HDAC4) and -28.27 ± 2.28 kcal/mol (HDAC7), identifying Valdiate as the most promising potential inhibitor.
CONCLUSION: Valdiate may serve as a potential inhibitor of mutant huntingtin-associated pathological pathways, pending further in-vitro and in-vivo validation.