Determination of Candidate Alternative Plant Actives for Dementia and Alzheimer’s Disease Proteins through Docking Studies

Year 2023, Volume: 27 Issue: 2, 255 - 265, 25.08.2023

Tuba Sevimoğlu , Vildan Atalay , Ayşenur Öztürk

Abstract

Alzheimer's disease (AD) is a common type of dementia, which is a progressive brain disorder causing memory, thought and behavioral issues.
Effective therapeutic treatments for AD and/or Dementia have not yet been developed. In this study select transcriptomic datasets were analyzed and disease
proteins that comply with selection criteria were identified. These proteins were then docked with Donepezil, Galantamine, Memantine and Rivastigmine drugs as
well as Thymus cilicius, Melissa officinalis, Salvia sclarea, Linum usitatissimum and Curcuma longa plant actives. Resulting binding energy values for mutant proteins
are significantly different from wild type, especially in MET (MET proto-oncogene, receptor tyrosine kinase) (PDB ID: 3ZXZ). The plant actives showed notable Relative
Stability values when docked with wild type proteins in comparison to drug molecules. To conclude, Alpha-Muurolene, Alpha-Atlantone, Alpha-Cadinene, BetaBourbonene, Beta-Cubebene and Germacrene-D as candidate alternative plant actives have been suggested for these diseases.

Keywords

Dementia, Alzheimer’s disease, Disease proteins, Plant actives, Drugs, Docking

Demans ve Alzheimer Hastalığı Proteinlerine Yönelik Aday Alternatif Bitki Aktiflerinin Kenetlenme Çalışmaları ile Belirlenmesi

Abstract

Alzheimer hastalığı (AD), hafıza, düşünce ve davranış sorunlarına neden olan ilerleyici bir beyin bozukluğu olan yaygın bir demans türüdür. AD ve/veya Demans
için etkili terapötik tedaviler henüz geliştirilememiştir. Bu çalışmada, bazı transkriptomik veri kümeleri analiz edilmiş ve seçim kriterlerine uyan hastalık
proteinleri belirlenmiştir. Bu proteinler Donepezil, Galantamine, Memantine ve Rivastigmine ilaçlarının yanı sıra Thymus cilicius, Melissa officinalis, Salvia sclarea,
Linum usitatissimum ve Curcuma longa bitki aktifleri ile kenetlenmiştir. Mutant proteinler için ortaya çıkan bağlanma enerjisi değerleri, özellikle MET'de (MET
proto-onkogen, reseptör tirozin kinaz) (PDB ID: 3ZXZ) olmak üzere, vahşi tipten önemli ölçüde farklıdır. Bitki aktif maddeleri, ilaç molekülleri ile karşılaştırıldığında
vahşi tip proteinlerle kenetlendiğinde dikkate değer Göreceli Stabilite değerleri göstermiştir. Sonuç olarak, bu hastalıklar için Alpha-Muurolene, Alpha-Atlantone,
Alpha-Cadinene, Beta-Bourbonene, Beta-Cubebene ve Germacrene-D aday alternatif bitki aktif maddeleri olarak önerilmiştir.

Keywords

Demans, Alzheimer hastalığı, Hastalık proteinleri, Bitki aktifleri, İlaçlar, Kenetlenme

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