Computational Analysis of Stilbenes as Potential Multi-Targeted Therapeutics for Alzheimer’s Disease

Abstract

Purpose: The aim of this study is to compare 13 stilbenes and 5 FDA-approved drugs used in the treatment of Alzheimer’s disease (AD) by ADME prediction and molecular docking method. Cholinergic, amyloid, tau, oxidative stress and inflammation hypotheses involved in AD pathology were targeted in molecular docking. Materials and Methods: SwissADME has been used to determine the physicochemical, lipophilicity, water solubility, pharmacokinetics, drug-likeness and medicinal chemistry properties of stilbenes (resveratrol, pterostilbene, oxyresveratrol, piceatannol, pinosylvin, isorhapontigenin, isorhapontin, astringin, piceid (polydatin), and mulberroside A) and FDA-approved drugs (tacrine, donepezil, rivastigmine, galantamine, and memantine). CBDOCK2 has been used to determine the binding affinity stilbenes and FDA-approved drugs to target proteins (AChE, BuChE, APP, BACE, GSK-3β, CDK5, SOD, CAT, GPx, Cox-2, iNOS, IL-1β, and TNF-α). Results: SWISS ADME results showed that stilbenes could be used as natural products in the treatment of AD. The molecular docking results indicated that mulberroside A showed the best vina score (kcal/mol) followed by astringin, piceid (polydatin), isorhapontin, donepezil, oxyresveratrol, piceatannol, galanthamine, resveratrol, isorhapontigenin, tacrine, pinosylvin, pterostilbene, rivastigmine, and memantine. Conclusion: Our study evaluated stilbenes and FDA-approved drugs for the treatment of AD using computational approaches. The results highlight its potential therapeutic effects on various hypotheses of AD pathology. More research is needed to validate these findings for clinical practice.

Keywords

• Alzheimer’s disease
• FDA-approved drugs
• molecular docking
• stilbene
• SWISS ADME.

Alzheimer Hastalığı için Potansiyel Çok Hedefli Terapötikler Olarak Stilbenlerin Hesaplamalı Analizi

Öz

Amaç: Bu çalışmanın amacı, 13 stilben ve Alzheimer hastalığı (AH)’nın tedavisinde kullanılan 5 Amerikan Gıda ve İlaç Dairesi onaylı ilacın ADME tahmini ve moleküler yerleştirme yöntemi ile karşılaştırılmasıdır. AD patolojisinde yer alan kolinerjik, amiloid, tau, oksidatif stres ve inflamasyon hipotezleri, moleküler yerleştirmede hedeflenmiştir. Gereç ve Yöntemler: SwissADME, stilbenlerin (resveratrol, pterostilben, oksiresveratrol, pikeatannol, pinosilvin, isorhapontigenin, isorhapontin, astringin, piceid (polidatin) ve mulberroside A) ve Amerikan Gıda ve İlaç Dairesi onaylı ilaçların (takrin, donepezil, rivastigmin, galantamin ve memantin) fizikokimyasal, lipofiliklik, suda çözünürlük, farmakokinetik, ilaca benzerlik ve tıbbi kimya özelliklerini belirlemek için kullanılmıştır. CBDOCK2, stilbenlerin ve Amerikan Gıda ve İlaç Dairesi onaylı ilaçların hedef proteinlere (AChE, BuChE, APP, BACE, GSK-3β, CDK5, SOD, CAT, GPx, Cox-2, iNOS, IL-1β ve TNF-α) bağlanma afinitesini belirlemek için kullanılmıştır. Bulgular: SWISS ADME sonuçları stilbenlerin AD tedavisinde doğal ürünler olarak kullanılabileceğini göstermiştir. Moleküler yerleştirme sonuçları, mulberroside A’nın en iyi vina skorunu (kcal/mol) gösterdiğini ve ardından astringin, piceid (polidatin), isorhapontin, donepezil, oxyresveratrol, piceatannol, galantamin, resveratrol, isorhapontigenin, takrin, pinosilvin, pterostilben, rivastigmin ve memantin’in geldiği gösterilmiştir. Sonuç: Çalışmamızda AH tedavisinde stilbenler ve Amerikan Gıda ve İlaç Dairesi onaylı ilaçlar hesaplamalı yaklaşımlar kullanılarak değerlendirilmiştir. Sonuçlar, AD patolojisinin çeşitli hipotezleri üzerindeki potansiyel terapötik etkilerini vurgulamıştır. Bu bulguların klinik uygulamalarda doğrulanması için daha fazla araştırmaya ihtiyaç vardır.

Anahtar Kelimeler

• Alzheimer hastalığı
• FDA onaylı ilaçlar
• moleküler yerleştirme
• stilben
• SWISS ADME.

Kaynakça

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