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

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.