In silico analysis of Naringenin and its O-alkyl derivatives for its potential binding with Estrogen Receptor- α

Abstract

Breast cancer remains the second-most significant cause of female mortality worldwide. The emergence of naturally occurring plant-derived compounds called phytoestrogens has aroused substantial interest in their potential to mitigate breast cancer. Phytoestrogens demonstrate structural similarities to human estrogen and can therefore interact with the estrogen receptors. Naringenin, an important flavonoid and phytoestrogen, has gathered significant attention in the field of cancer due to its potential anti-inflammatory and antioxidant properties while its O-alkyl derivatives can enhance its bioavailability and target specificity. In this study, we have screened Naringenin and four of its O-alkyl derivatives, namely Isosakuranetin, 5-O-Methylnaringenin, Sakuranetin and 4',7-Di-O-methylnaringenin for their binding affinity with estrogen receptor-α (PDB ID: 6VJD). Molecular docking studies targeting estrogen receptor-α (PDB ID: 6VJD) revealed favorable binding energies and interaction patterns for naringenin and its derivatives, suggesting potential as therapeutic agents against breast cancer. Additionally, analysis with SwissADME highlighted the compounds' permeability across the blood-brain barrier (BBB), high absorption rates and water solubility, emphasizing their potential for therapeutic applications beyond breast cancer. Furthermore, the compounds exhibited promising pharmacokinetic profiles, synthetic accessibility and adherence to Lipinski's rule of five, supporting their candidacy for further development as therapeutic agents.