Inhibition of Breast Cancer Proteins by the Flavonoid Naringenin and its Derivative: A Molecular Docking Study

Abstract

Cancer is a multifaceted disease and is a major health burden in the world. Breast cancer is leading cause of mortality among women worldwide. Plant derived compounds have also been used in the treatment of cancer. Amongst them, flavonoids have been well documented for their therapeutic potential against cancer cells. Naringenin is a flavanone abundantly available in grapefruit and tomato among other sources. Several natural and synthetic derivatives of naringenin have been reported for anticancer activity. In this study, naringenin (Nar) and its derivative, naringenin 2-hydroxy benzoyl hydrazone (Nar-Bhz) were studied for their inhibitory potential against proteins involved in breast cancer. Molecular docking simulation by AutoDock was utilized to investigate the interaction of Nar and Nar-Bhz with Survivin, Estrogen receptor ? (ER?), progesterone receptor (PR), Akt1, and Epidermal growth factor receptor (EGFR). Doxorubicin was used as positive control because of its clinical importance in breast cancer treatment. Discovery Studio Visualizer was used to visualize the interactions and the docking results showed that the protein ligand complexes were stabilized by hydrogen bonding and hydrophobic interactions. The binding energies ranged between -7.66 to -7.91 kcal/mol with Nar-Bhz and between -5.49 and -11.05 kcal/mol for Nar. Significant inhibition constant was observed for Nar-Bhz interaction with Akt1 and EGFR. Also, several residues of Akt1 interacted with both the ligands. It can be concluded that naringenin and its derivative have promising inhibitory potential against the breast cancer proteins. The findings of this study may pave the way for detailed exploration of naringenin as breast cancer drug and as a nutraceutical or dietary supplement in daily intake.