Biyoaktif Bileşiklerden Yararlanma: Östrojen Reseptörüyle İlişkili Patolojilerde Hesperidin ve Türevleri

Abstract

Amaç: Hesperidin ve türevleri olan hesperetin, diosmin, diosmetin ve neohesperidin, ağırlıklı olarak narenciye meyvelerinde bulunan biyoaktif bileşiklerdir. Bu bileşikler, özellikle östrojen reseptörüyle ilişkili hastalıklardaki potansiyel terapötik etkileri nedeniyle önemli ölçüde ilgi görmektedir. Bu çalışma, hesperidin ve türevlerinin östrojen reseptör alfa (ER-α) ile olan bağlanma afinitelerini ve etkileşim mekanizmalarını moleküler docking (bağlanma simülasyonu) teknikleri kullanarak değerlendirmeyi amaçlamaktadır. Yöntemler: Hesperidin türevlerinin ER-α ile bağlanma enerjilerini belirlemek amacıyla moleküler docking simülasyonları gerçekleştirilmiştir. Ayrıca, biyoyararlanım, kan-beyin bariyeri geçirgenliği ve bağırsak emilimi gibi farmakokinetik özellikleri değerlendirmek için ADMET (Emilim, Dağılım, Metabolizma, Atılım ve Toksisite) analizi yapılmıştır. Bulgular: Diosmin, türevler arasında en yüksek bağlanma afinitesini göstermiş ve bu değeriyle standart bir anti-kanser ilacı olan Tamoksifen’e yakın bir bağlanma enerjisi elde etmiştir. Ancak, biraz daha düşük bağlanma enerjisi klinik etkinliğini etkileyebilir. Neohesperidin umut verici bir bağlanma afinitesi göstermiştir, ancak zayıf bağırsak emilimi nedeniyle biyoyararlanımı sınırlıdır. ADMET analizi, bu flavonoidlerin genel olarak olumlu farmakokinetik özelliklere sahip olduğunu, ancak zayıf kan-beyin bariyeri geçirgenliği ve değişken emilim oranları gibi bazı etkenlerin terapötik etkinliklerini sınırlayabileceğini ortaya koymuştur. Sonuç: Belirli farmakokinetik zorluklara rağmen, hesperidin ve türevleri ER-α ile umut verici etkileşimler sergilemekte olup, Tamoksifen'e alternatif veya tamamlayıcı tedavi seçenekleri olarak potansiyele sahiptir.

Keywords

• Hesperidin
• Diosmin
• Östrojen Reseptörü
• Moleküler Docking
• Farmakokinetik
• Biyoyararlanım

Harnessing Bioactive Compounds: Hesperidin and Its Derivatives in Estrogen Receptor-Related Pathologies

Abstract

Aim: Hesperidin and its derivatives, including hesperetin, diosmin, diosmetin, and neohesperidin, are flavonoids predominantly found in citrus fruits. These compounds have gained significant interest due to their potential therapeutic effects, particularly in estrogen receptorrelated diseases. This study aims to evaluate the binding affinities and interaction mechanisms of hesperidin and its derivatives with estrogen receptor alpha (ER-α) using molecular docking techniques. Methods: Molecular docking simulations were performed to determine the binding energies of hesperidin derivatives with ER-α. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis was conducted to evaluate pharmacokinetic properties, including bioavailability, blood-brain barrier permeability, and intestinal absorption. Results: Diosmin exhibited the highest binding affinity among the derivatives, with a binding energy comparable to Tamoxifen, a standard anti-cancer drug. However, its slightly lower binding energy may affect its clinical efficacy. Neohesperidin demonstrated promising affinity but had poor intestinal absorption, limiting its bioavailability. ADMET analysis revealed that while these flavonoids generally have favorable pharmacokinetic properties, factors such as poor blood-brain barrier permeability and variable absorption rates may restrict their therapeutic effectiveness. Conclusion: Despite certain pharmacokinetic challenges, hesperidin and its derivatives exhibit promising interactions with ER-α, suggesting their potential as alternative or adjunct therapies to Tamoxifen.

Keywords

• Hesperidin
• Diosmin
• Estrogen Receptor
• Molecular Docking
• Pharmacokinetics
• Bioavailability

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