Alzheimer Hastalığında İlacın Yeniden Kullanım İçin Hesaplamalı Yaklaşımlar

Abstract

Alzheimer's disease a progressive age-related brain disorder. It causes gradual memory loss, changes in personality traits, confusion, impaired thinking, and mood changes Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor have been choiced for the treatment of Alzheimer’s disease. Dual cholinesterase inhibitors have become a new hotspot in the investigation of anti-Alzheimer's drugs. The current study was designed to identify inhibitors for both AChE and BuChE enzymes using computational approaches to accelerate the process of identifying an effective treatment for Alzheimer. From the available drugs, we selected families of aspirin and imatinib. After the adoption of molecular docking, we found that fendosal from aspirin group and Flumatinib from Imatinib group are the most active compounds. The docking scores for fendosal was -8.160 kcal/mol against AChE while Flumatinib was -9.433 kcal/mol with BuChE and -9.541 kcal/mol AChE. The 10 ns molecular dynamics simulation for fendosal and flumatinib against AChE and BuChE was performed to evaluate the drug's ability to remain stable within the binding sites of AChE and BuChE with the aid of RMSD and RMSF plots. These results revealed that Flumatinib and fendosal are good inhibitors for both BuChE and AChE, which could be used in vivo and in vitro studies for improving outcomes.