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

Öz

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.

Anahtar Kelimeler

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

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

Öz

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.

Anahtar Kelimeler

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

Kaynakça

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