In-vitro, Bioinformatics and Computational Biophysical Analyses of Antifungal Phytochemicals from Acalypha wilkesiana Variants Targeting Malassezia Lipase
DOI:
https://doi.org/10.26538/tjdr/v2i9.3Keywords:
Seborrheic dermatitis, Malassezia globosa, Acalypha wikesiana, Lipase inhibition, Molecular dockingAbstract
Purpose: Seborrheic dermatitis (SD) is a common chronic inflammatory skin disorder, often associated with the activity of lipid-hydrolyzing enzymes secreted by Malassezia globosa. Conventional antifungals often show limited efficacy and adverse effects, while the mechanisms underlying traditional remedies like Acalypha wilkesiana remain underexplored.
Methods: This study evaluated the antifungal potential of phytochemicals derived from the red and green variants of A. wikesiana, targeting M. globosa lipase (PDB ID: 3UUE). Crude ethanol extracts were analyzed via gas chromatography–mass spectrometry (GC-MS), and preliminary in-vitro antifungal activity was assessed against M. globosa. Identified compounds were subjected to molecular docking and molecular dynamics (MD) simulations to assess binding affinity and stability. ADMET profiling and density functional theory (DFT) calculations were employed to predict pharmacokinetics, toxicity, and electronic reactivity.
Results: The red A. wikesiana extract demonstrated strong antifungal activity, producing a 60 mm inhibition zone, while the green variant was inactive. Molecular docking identified aspidospermidin-17-ol, 1-acetyl-19,21-epoxy-15,16-dimethoxy- (ASP) as the top-performing compound with a binding affinity of –6.8 kcal/mol, outperforming ketoconazole and the native ligand. MD simulations confirmed the structural stability of the ASP–lipase complex, exhibiting minimal RMSD fluctuations. ADMET predictions indicated low dermal and systemic toxicity, and DFT analysis confirmed favorable electronic properties.
Conclusion: The findings highlight ASP from red A. wikesiana as a potent and safe inhibitor of M. globosa lipase, supporting its potential development as a novel, plant-based topical antifungal agent for the management of seborrheic dermatitis.
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