Yıl 2020, Cilt 44 , Sayı 1, Sayfalar 18 - 32 2020-01-31

Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.
YENİ TAKRİN VE HESPERETİN ANALOGLARI: ALZHEİMER HASTALIĞINDA POTANSİYEL ASETİLKOLİN ESTERAZ İNHİBİTÖRLERİNİN AYDINLATILMASI İÇİN TASARIM, MOLEKÜLER DOKİNG VE İN SİLİKO ADME ÇALIŞMALARI

Naresh KONDAPALLI [1] , Kanna SRUTHI [2]


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.

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.

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  • 8. Schrödinger Release 2017-3: QikProp, Schrödinger, LLC, New York, NY, 2017.
Birincil Dil en
Konular Farmakoloji ve Eczacılık
Bölüm Araştırma Makalesi
Yazarlar

Orcid: 0000-0002-6454-5291
Yazar: Naresh KONDAPALLI (Sorumlu Yazar)
Kurum: G. Pulla Reddy College of Pharmacy, Hyderabad, Telangana, India
Ülke: India


Yazar: Kanna SRUTHI
Kurum: Department of Pharmaceutical Chemistry R.B.V.R.R Women’s College of Pharmacy, Osmania University
Ülke: India


Tarihler

Yayımlanma Tarihi : 31 Ocak 2020

Bibtex @araştırma makalesi { jfpanu559509, journal = {Journal of Faculty of Pharmacy of Ankara University}, issn = {1015-3918}, eissn = {2564-6524}, address = {Ankara University Faculty of Pharmacy Degol Str. TR-06100 Tandogan/Ankra/TURKEY}, publisher = {Ankara Üniversitesi}, year = {2020}, volume = {44}, pages = {18 - 32}, doi = {10.33483/jfpau.559509}, title = {Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.}, key = {cite}, author = {KONDAPALLI, Naresh and SRUTHI, Kanna} }
APA KONDAPALLI, N , SRUTHI, K . (2020). Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.. Journal of Faculty of Pharmacy of Ankara University , 44 (1) , 18-32 . DOI: 10.33483/jfpau.559509
MLA KONDAPALLI, N , SRUTHI, K . "Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.". Journal of Faculty of Pharmacy of Ankara University 44 (2020 ): 18-32 <https://dergipark.org.tr/tr/pub/jfpanu/issue/52196/559509>
Chicago KONDAPALLI, N , SRUTHI, K . "Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.". Journal of Faculty of Pharmacy of Ankara University 44 (2020 ): 18-32
RIS TY - JOUR T1 - Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease. AU - Naresh KONDAPALLI , Kanna SRUTHI Y1 - 2020 PY - 2020 N1 - doi: 10.33483/jfpau.559509 DO - 10.33483/jfpau.559509 T2 - Journal of Faculty of Pharmacy of Ankara University JF - Journal JO - JOR SP - 18 EP - 32 VL - 44 IS - 1 SN - 1015-3918-2564-6524 M3 - doi: 10.33483/jfpau.559509 UR - https://doi.org/10.33483/jfpau.559509 Y2 - 2019 ER -
EndNote %0 Ankara Üniversitesi Eczacılık Fakültesi Dergisi Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease. %A Naresh KONDAPALLI , Kanna SRUTHI %T Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease. %D 2020 %J Journal of Faculty of Pharmacy of Ankara University %P 1015-3918-2564-6524 %V 44 %N 1 %R doi: 10.33483/jfpau.559509 %U 10.33483/jfpau.559509
ISNAD KONDAPALLI, Naresh , SRUTHI, Kanna . "Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.". Journal of Faculty of Pharmacy of Ankara University 44 / 1 (Ocak 2020): 18-32 . https://doi.org/10.33483/jfpau.559509
AMA KONDAPALLI N , SRUTHI K . Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.. Ankara Ecz. Fak. Derg.. 2020; 44(1): 18-32.
Vancouver KONDAPALLI N , SRUTHI K . Novel Tacrine and Hesperetin analogues: Design, Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease.. Journal of Faculty of Pharmacy of Ankara University. 2020; 44(1): 32-18.