MOLECULAR INTERACTION AND COMPUTATIONAL EVALUATION OF ANLE138B AS AN INHIBITOR OF Α-SYNUCLEIN AGGREGATION IN PARKINSON’S DISEASE
DOI:
https://doi.org/10.65327/bp.v12i1.2527Keywords:
Parkinson’s disease, α-synuclein, Anle138b, molecular docking, ADMETAbstract
Parkinson’s disease is a progressive neurodegenerative disorder strongly associated with the misfolding and aggregation of α-synuclein, making this protein an important target for disease-modifying therapeutic strategies. This study computationally evaluated Anle138b as a potential α-synuclein-targeting compound using molecular docking, interaction analysis, physicochemical profiling, ADME prediction, and toxicity assessment. Molecular docking identified a best-ranked binding pose with an affinity of −9.456 kcal/mol, supported by multiple non-covalent interactions, including aromatic, electrostatic, and hydrogen-bond-associated contacts. Physicochemical analysis showed a molecular weight of 342.00 g/mol, TPSA of 47.14 Ų, logP of 4.44, and limited molecular flexibility. ADME prediction indicated a high blood–brain barrier probability of 0.987, supporting potential central nervous system accessibility. However, toxicity prediction revealed comparatively high probabilities for drug-induced liver injury, carcinogenicity, neurotoxicity, and respiratory toxicity. Overall, Anle138b demonstrated favorable predicted binding and CNS-relevant pharmacokinetic characteristics, but its potential safety liabilities require further investigation. Molecular dynamics simulations, free-energy calculations, aggregation assays, neuronal toxicity studies, and in vivo validation are recommended to confirm its therapeutic potential against α-synuclein-associated pathology in Parkinson’s disease.
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Copyright (c) 2026 Dr. Damilola Alex Omoboyowa, Dr. Toheeb Adewale Balogun
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