DOI: 10.26453/otjhs.1753751 ISSN: 2459-1467

The Determination of Druglikeness, Pharmacokinetic Profile, Toxicity Parameters, and Anti-Alzheimer Activity of Amiloride: A Detailed in silico Investigation

Ziya Çakır, Çiğdem Bilkan, Burhan Ertekin, Mustafa Tuğfan Bilkan
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Objective: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by complex molecular mechanisms, including amyloid-β accumulation and synaptic dysfunction. In this context, the present study aimed to perform a comparative in silico evaluation of amiloride and memantine in terms of their interactions with ASIC, along with their pharmacokinetic and toxicity-related properties. Materials and Methods: The structural and pharmacokinetic properties of amiloride and memantine were assessed using in silico approaches, including molecular docking, ADME prediction, and toxicity profiling. Molecular docking analyses were performed against the ASIC receptor (PDB ID: 2QTS) using Molegro Virtual Docker. Drug-likeness and pharmacokinetic parameters were evaluated based on established computational platforms, and toxicity endpoints were predicted using in silico toxicity models. Results: Docking analysis indicated that amiloride exhibited a higher predicted binding affinity for the ASIC receptor than memantine. Both compounds complied with Lipinski’s rule of five, suggesting acceptable drug-likeness. In silico ADME predictions revealed differences in pharmacokinetic behavior, particularly in blood–brain barrier permeability, with amiloride showing limited central nervous system penetration compared to memantine. Toxicity predictions suggested that both compounds possess mixed safety profiles, with varying probabilities across different toxicity endpoints. Conclusion: The present in silico findings suggest that amiloride may interact more favorably with the ASIC receptor compared to memantine under computational conditions. However, given the predictive nature of the employed methods, these results should be interpreted cautiously. Overall, amiloride may represent a potential lead compound for further experimental investigation in ASIC-related mechanisms of Alzheimer’s disease.

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