Formononetinin Potansiyel Bir Anti-Obezite Ajanı Olarak Hesaplamalı (In Silico) Değerlendirilmesi: Kuantum Kimyasal ve Doking Analizleri

Abstract

Formononetin, doğal bir polifenolik bileşik, obezite tedavisi için umut verici bir aday olarak ortaya çıkmıştır. Bu çalışma, formononetinin elektronik yapısını, protein-ligand etkileşimlerini ve farmakokinetik özelliklerini araştırmak için çok katmanlı bir hesaplamalı yaklaşım kullanmıştır. PM3 yöntemi kullanılarak yapılan kuantum kimyasal hesaplamalar, formononetinin yüksek kimyasal stabiliteye ve düşük reaktiviteye sahip olduğunu, geniş bir HOMO-LUMO enerji aralığı (ΔE = 8.319 eV), yüksek elektronegatiflik (4.748 eV) ve kimyasal sertlik (4.160 eV) gösterdiğini ortaya koymuştur. Yağ kütlesi ve obezite ile ilişkili protein (FTO) üzerinde yapılan moleküler yerleştirme simülasyonları, −7.70 kcal/mol'lük bir bağlanma afinitesi göstermiş, hidrofobik etkileşimler, hidrojen bağları ve π-katyon etkileşimleri kararlı ligand-protein kompleksine katkıda bulunmuştur. ADME analizi, formononetinin yüksek gastrointestinal emilim, orta düzeyde lipofilite ve ilaç benzeri kurallara uyum gibi olumlu ilaç benzeri özellikler sergilediğini göstermiştir. Ancak, düşük suda çözünürlüğü ve P-glikoprotein efflüksü potansiyeli daha fazla optimizasyon gerektirebilir. Genel olarak, bu çalışma formononetinin anti-obezite ajanı olarak potansiyelini vurgulamakta ve hesaplamalı yaklaşımlar kullanarak doğal ürün bazlı obezite terapötiklerinin keşfi için teorik olarak temellendirilmiş bir çerçeve sunmaktadır.

Keywords

• Formononetin
• Anti-obezite
• Kuantum kimyasal hesaplamalar
• Moleküler kenetleme
• ALKBH5 Enzim
• ADME özellikleri

In Silico Evaluation of Formononetin as a Potential Anti-Obesity Agent: Quantum Chemical and Docking Insights

Abstract

Obesity is a growing global health concern and a major risk factor for various chronic diseases. This study employed a range of in silico computational approaches to evaluate the potential anti-obesity effects of formononetin, a natural bioactive compound. Quantum chemical analyses indicated that formononetin possesses a stable electronic structure and is well-suited for interactions with biological targets. Molecular docking results revealed that formononetin exhibits strong and favourable binding interactions with the ALKBH5 enzyme, which plays a role in epigenetic mechanisms associated with obesity. Additionally, the ADME assessment revealed that formononetin exhibits drug-like properties and high gastrointestinal absorption, although certain limitations related to solubility and transport mechanisms may impact its bioavailability. Overall, the findings suggest that formononetin is a promising candidate for managing metabolic disorders and reinforce the therapeutic potential of natural compounds in multi-targeted obesity treatments.

Keywords

• Formononetin
• Anti-obesity
• Quantum chemical calculations
• Molecular docking
• ALKBH5 enzyme
• ADME properties.

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