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

Naresh Kondapallı; Kanna Sruthı

doi:10.33483/jfpau.559509

Research Article

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

Year 2020, Volume: 44 Issue: 1, 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

References

1. Alzheimer’s Association. Alzheimer’s disease Facts and Figures (2018). Alzheimer’s Dement; 14(3), 367-429. Retrieved from https://www.alzheimersanddementia.com/article/S1552-5260(18)30041-4/abstract
2. Ortman, J.M., Velkoff, V.A., Hogan, H. (2014). An Aging Nation: The Older Population in the United States, Current Population Reports, U.S. Census Bureau, Washington, D.C., 25-1140. Retieved from https://www.census.gov/prod/2014pubs/p25-1140.pdf.
3. Haibin, L., Lirong, W., Weiwei, S., &Xiang-QunX. (2014). Advances in recent patent and clinical trial drug development for Alzheimer’s disease, Pharmaceutical Patent Analyst, 3(4), 429-447.
4. Snezana, A., Kustrin, C., Kettle, D., &Morton, W. (2018). A molecular approach in drug development for Alzheimer’s disease, Biomedicine&Pharmacotherapy, 106, 553-565.
5. Parhiz, H., Roohbakhsh, A., Soltani, F., Rezaee, R., & Iranshahi, M. (2014). Antioxidant and Anti-Inflammatory Properties of the Citrus Flavonoids Hesperidin and Hesperetin: An Updated Review of their Molecular Mechanisms and Experimental Models. Phytotherapy Research, 29(3), 323–331. doi: 10.1002/ptr.5256
6. Hajialyani, M., Farzaei, M. H., Echeverría, J., Nabavi, S., Uriarte, E., & Sobarzo-Sánchez, E. (2019). Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence. Molecules, 24(3), 648. doi: 10.3390/molecules24030648
7. Schrödinger Release 2017-3: Glide, Schrödinger, LLC, New York, NY, 2017.
8. Schrödinger Release 2017-3: QikProp, Schrödinger, LLC, New York, NY, 2017.

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

Year 2020, Volume: 44 Issue: 1, 18 - 32, 31.01.2020

Naresh Kondapallı , Kanna Sruthı

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

Cited By: 1

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

References

1. Alzheimer’s Association. Alzheimer’s disease Facts and Figures (2018). Alzheimer’s Dement; 14(3), 367-429. Retrieved from https://www.alzheimersanddementia.com/article/S1552-5260(18)30041-4/abstract
2. Ortman, J.M., Velkoff, V.A., Hogan, H. (2014). An Aging Nation: The Older Population in the United States, Current Population Reports, U.S. Census Bureau, Washington, D.C., 25-1140. Retieved from https://www.census.gov/prod/2014pubs/p25-1140.pdf.
3. Haibin, L., Lirong, W., Weiwei, S., &Xiang-QunX. (2014). Advances in recent patent and clinical trial drug development for Alzheimer’s disease, Pharmaceutical Patent Analyst, 3(4), 429-447.
4. Snezana, A., Kustrin, C., Kettle, D., &Morton, W. (2018). A molecular approach in drug development for Alzheimer’s disease, Biomedicine&Pharmacotherapy, 106, 553-565.
5. Parhiz, H., Roohbakhsh, A., Soltani, F., Rezaee, R., & Iranshahi, M. (2014). Antioxidant and Anti-Inflammatory Properties of the Citrus Flavonoids Hesperidin and Hesperetin: An Updated Review of their Molecular Mechanisms and Experimental Models. Phytotherapy Research, 29(3), 323–331. doi: 10.1002/ptr.5256
6. Hajialyani, M., Farzaei, M. H., Echeverría, J., Nabavi, S., Uriarte, E., & Sobarzo-Sánchez, E. (2019). Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence. Molecules, 24(3), 648. doi: 10.3390/molecules24030648
7. Schrödinger Release 2017-3: Glide, Schrödinger, LLC, New York, NY, 2017.
8. Schrödinger Release 2017-3: QikProp, Schrödinger, LLC, New York, NY, 2017.

There are 8 citations in total.

Details

Primary Language	English
Subjects	Pharmacology and Pharmaceutical Sciences
Journal Section	Research Article
Authors	Naresh Kondapallı 0000-0002-6454-5291 Kanna Sruthı This is me
Publication Date	January 31, 2020
Submission Date	April 30, 2019
Acceptance Date	September 23, 2019
Published in Issue	Year 2020 Volume: 44 Issue: 1

Cite

APA	Kondapallı, N., & Sruthı, 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. https://doi.org/10.33483/jfpau.559509
AMA	Kondapallı N, Sruthı 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. J. Fac. Pharm. Ankara. January 2020;44(1):18-32. doi:10.33483/jfpau.559509
Chicago	Kondapallı, Naresh, and Kanna Sruthı. “ 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, no. 1 (January 2020): 18-32. https://doi.org/10.33483/jfpau.559509.
EndNote	Kondapallı N, Sruthı K (January 1, 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.
IEEE	N. Kondapallı and K. Sruthı, “ Molecular docking and in silico ADME studies to identify potential Acetyl choline esterase inhibitors for Alzheimer’s disease”., J. Fac. Pharm. Ankara, vol. 44, no. 1, pp. 18–32, 2020, doi: 10.33483/jfpau.559509.
ISNAD	Kondapallı, Naresh - Sruthı, Kanna. “ 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 (January 2020), 18-32. https://doi.org/10.33483/jfpau.559509.
JAMA	Kondapallı N, Sruthı 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. J. Fac. Pharm. Ankara. 2020;44:18–32.
MLA	Kondapallı, Naresh and Kanna Sruthı. “ 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, vol. 44, no. 1, 2020, pp. 18-32, doi:10.33483/jfpau.559509.
Vancouver	Kondapallı N, Sruthı 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. J. Fac. Pharm. Ankara. 2020;44(1):18-32.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.