Akinbo et al., J Biomed & App Sci FUD (2025) 4:1
Keywords: Alzheimer's Disease, Computer-aided drug design, Complex mechanism, Binding energy, Pharmacokinetics.
2025-10-03 DOI: Akinbo et al., JOBASFUD_2024_3_2_016
Background: Alzheimer's disease (AD), a progressive neurodegenerative disorder affecting cognitive functions, remains a critical medical challenge with limited treatment options and significant side effects. This study explores the potential of novel piperazine-containing hydrazone derivatives as acetylcholinesterase inhibitors, targeting a key enzymatic pathway implicated in AD progression. Methods: A structure-based drug design approach was adopted to identify and synthesize hydrazone derivatives. The study utilized the protein target 4EY7, recognized for its relevance in AD, with molecular docking and pharmacokinetic evaluations to optimize compound interaction and binding efficiency. Results: Fifteen hydrazone derivatives demonstrated enhanced binding interactions, stability, and superior drug-like properties compared to the reference compound. A lead compound with a binding energy of -27.23 kcal/mol showed the highest affinity and pharmacological promise, surpassing the reference compound, galantamine, in molecular docking analyses. Conclusion: The findings suggest that these hydrazone derivatives represent a promising class of multifunctional inhibitors with potential therapeutic applications in AD. Further investigations are warranted to validate their efficacy and safety in preclinical and clinical settings.