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Computational Approaches for Drug Repurposing in Alzheimer's Disease
Abstract
Alzheimer's disease is 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) inhibitors have been chosen 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 the aspirin and imatinib. After the adoption of molecular docking, we found that fendosal from aspirin group and Flumatinib from the Imatinib group are the most active compounds. The docking scores for fendosal was -8.160 kcal/mol against AChE while Flumatinib had -9.433 kcal/mol and -9.541 kcal/mol scores with BuChE and AChE, respectively. 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 to improve outcomes.
Keywords
Kaynakça
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Ayrıntılar
Birincil Dil
İngilizce
Konular
Yapısal Biyoloji
Bölüm
Araştırma Makalesi
Yayımlanma Tarihi
30 Aralık 2022
Gönderilme Tarihi
23 Mart 2022
Kabul Tarihi
9 Mayıs 2022
Yayımlandığı Sayı
Yıl 2022 Cilt: 25 Sayı: Ek Sayı 2
