Computational Approaches for Drug Repurposing in Alzheimer's Disease

Zaid Jaafar Awad Al-nuaimi; Abuzer Çelekli; Tugba Taskın Tok

doi:10.18016/ksutarimdoga.vi.1092038

EN TR

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

Alzheimer Hastalığında İlacın Yeniden Kullanım İçin Hesaplamalı Yaklaşımlar

Öz

Alzheimer hastalığı, ilerleyici, yaşa bağlı bir beyin hastalığıdır. Kademeli hafıza kaybına, kişilik özelliklerinde değişikliklere, kafa karışıklığına, düşünme bozukluğuna ve ruh hali değişikliklerine neden olur. Alzheimer hastalığının tedavisi için asetilkolinesteraz (AChE) ve butirilkolinesteraz (BuChE) inhibitörü seçilmiştir. Çift kolinesteraz inhibitörleri, anti-Alzheimer ilaçlarının araştırılmasında yeni bir etkin nokta haline geldi. Bu çalışma, Alzheimer için etkili bir tedavi tanımlama sürecini hızlandırmak için hesaplama yaklaşımlarını kullanarak AChE ve BuChE enzimlerine yönelik inhibitörlerin belirlemesi için tasarlanmıştır. Mevcut ilaçlardan aspirin ve imatinib aileleri seçilmiştir. Moleküler yerleştirmenin benimsenmesinden sonra, aspirin grubundan fendosalın ve Imatinib grubundan flumatinib'in en etkin bileşikler olduğu bulunmuştur. Fendosal için kenetlenme skorları AChE'ye karşı -8,160 kcal/mol iken Flumatinib BuChE ve AChE ile sırasıyla -9,433 kcal/mol ve -9.541 kcal/mol skorlarına sahip olmuştur. AChE ve BuChE'ye karşı fendosal ve flumatinib için 10 ns moleküler dinamik simülasyonu, RMSD ve RMSF grafiklerinin yardımıyla ilacın AChE ve BuChE'nin bağlanma bölgeleri içinde stabil kalma kabiliyetini değerlendirmek için yapılmıştır. Bu sonuçlar, Flumatinib ve fendosal'ın hem BuChE hem de AChE için iyi bir inhibitör olduğunu ortaya koymuş olup sonuçların geliştirilmesi için in vivo ve in vitro çalışmaların kullanılabilir.

Anahtar Kelimeler

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Details

Primary Language

English

Subjects

Structural Biology

Journal Section

Research Article

Authors

Zaid Jaafar Awad Al-nuaimi
0000-0003-4585-2488
Iraq

Abuzer Çelekli ^*
0000-0002-2448-4957
Türkiye

Tugba Taskın Tok
0000-0002-0064-8400
Türkiye

Publication Date

December 30, 2022

Submission Date

March 23, 2022

Acceptance Date

May 9, 2022

Published in Issue

Year 2022 Volume: 25 Number: Ek Sayı 2

DOI

https://doi.org/10.18016/ksutarimdoga.vi.1092038

IZ

https://izlik.org/JA59XX46CJ

Cite

RIS / Bibtex

APA

Al-nuaimi, Z. J. A., Çelekli, A., & Taskın Tok, T. (2022). Computational Approaches for Drug Repurposing in Alzheimer’s Disease. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 25(Ek Sayı 2), 307-315. https://doi.org/10.18016/ksutarimdoga.vi.1092038