Parkinson Hastalığında Çift Modülatör olarak Desmodium gangeticum Bileşiklerinin Silico Karakterizasyonunda MAO-B ve 5-HT2A: Moleküler Bağlama, ADMET Profilleme, MM-GBSA, QSAR Modelleme ve Moleküler Dinamik Simülasyonunu Birleştiren Entegre Bir Yaklaşım

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Abstract Management of Parkinson's disease (PD) is challenging: dopaminergic treatments alleviate motor symptoms but exacerbate psychosis, while antipsychotics alleviate hallucinations but exacerbate motor symptoms. To tackle this problem, we combined the in-silico profiling of Desmodium gangeticum's phytochemicals with dual monoamine oxidase‑B (MAO‑B) and 5‑hydroxytryptamine type 2A (5‑HT2A) modulating activity. Docking studies suggested Desmodin and 5,7,2′,4′‑Tetrahydroxy‑6‑prenylisoflavanone as potential MAO‑B modulators and N, N‑Dimethyltryptamine and Tryptamine as 5‑HT2A modulators. ADMET profiling revealed promising central nervous system (CNS) drug-likeness, adequate blood-brain barrier penetration and tolerability. Toxicity prediction showed non-toxicity towards hepatotoxicity, mutagenicity and carcinogenicity. MM-GBSA calculations and molecular dynamics studies supported strong interactions and AutoQSAR indicated bioactivity. Thus, these findings indicate that metabolites of D. gangeticum are potentially effective bi-therapy molecules to treat the motor and neuropsychiatric symptoms of PD. These phytochemicals need experimental research to advance their development as safer and multi‑targeted drug candidates for clinical trials.

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