YENİ TAKRİN VE HESPERETİN ANALOGLARI: ALZHEİMER HASTALIĞINDA POTANSİYEL ASETİLKOLİN ESTERAZ İNHİBİTÖRLERİNİN AYDINLATILMASI İÇİN TASARIM, MOLEKÜLER DOKİNG VE İN SİLİKO ADME ÇALIŞMALARI

Year 2020, , 18 - 32, 31.01.2020

Naresh Kondapallı , Kanna Sruthı

https://doi.org/10.33483/jfpau.559509

Cited By: 1

Abstract

Amaç: Mevcut araştırma,
Alzheimer hastalığını tedavi etmek için Tacrin ve Hesperetin yapılarından
moleküler modifikasyonla yeni potansiyel moleküller tasarlamayı ve belirlemeyi
amaçlamaktadır. Asetilkolinesteraz (AChE) enzimi hedef olarak seçilmiştir,
çünkü AChE inhibitörleri demansın tedavisinde ve diğer semptomların
hafifletilmesinde başarılı olmuştur.

Gereç ve Yöntem: Bu
çalışmada, asetilkolinesteraz (AChE) inhibitörlerinin yapısal
özelliklerinitemel alan iki seri yeni Takrin (T1-T9) ve Hesperetin(H1-H9)
türevleri tasarlanmış ve AChE (PDB ID: 1DX4) üzerinde Anti-Alzheimer ilaç
olarak potansiyel türevler belirlemek için ekstra hassasdoking uygulaması ile
GLIDE kullanarak taranmıştır. Doking sonuçları (Glide skoru, XP skoru, doking
skoru ve bağlanma etkileşimleri) standart ilaç, Takrin ile karşılaştırıldı.

Sonuç
ve Tartışma: Doking sonuçlarından, T9'un tasarlanan bileşikler arasında en yüksek
doking skoru gösterdiği bulundu. ADME özellikleri ayrıca Qikprop uygulaması
kullanılarak da öngörülmüş, yukarıdaki çalışmalardan en yüksek AChE inhibisyonuna
sahip potansiyel analoglar ve mükemmel farmakokinetik özellikleri
tanımlanmıştır.

Keywords

Alzheimer hastalığı (AD), asetilkolinesteraz inhibitörleri (AChE), glide, takrin

Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.

Abstract

Alzheimer’s disease is
considered as most prevailing and common CNS disease found in elder population
over 60 years of age. The early diagnosis of the disease prior to the
occurrence of first behavioral symptom, dementia is difficult and hence the
management of dementia and alleviation of other symptoms is the only available
treatment for the AD. Acetyl cholinesterase inhibitors (AchE) are widely used
in the treatment.   In this study two series of new Tacrine(T1-T9)
and Hesperetin derivatives(H1-H9) on the basis of the structural
characteristics of acetyl cholinesterase (AchE) inhibitors were designed and screened
to identify potential analogues as Anti-Alzheimer drug on the AchE (PDB ID:1DX4)   using GLIDE employing extra-precision
docking. The docking results Glide score, XPscore, docking score and binding interactions
were compared with standard drug Tacrine. From the docking results it was found
that T9 showed highest docking score among the designed compounds. The ADME
properties also predicted using Qikprop application, from the above studies
potential analogues with highest AchE inhibition and excellent pharmacokinetic
properties were identified.

Keywords

Alzheimer’s Disease (AD), Acetylcholine esterase inhibitors(AchE), Glide, tacrine

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