Molecular docking studies of phytochemicals of pomegranate as anti-breast cancer agents

Abstract

Breast cancer is second most common cancer type in the world amd scientists have been moving towards natural phytochemicals as an anti-cancer agent because most anti-cancer drugs affect other healthy cells. One such natural source is pomegranate (Punica granatum). It contains several phytochemicals: namely, ellagic acid, ellagic acid-4-O-xylopyranoside, gallic acid, vanillic acid, (+)- catechin, quercitrin, and citric acid. Recent research studies have pointed out that these polyphenols posses strong anti-cancer activity through a variety of mechanisms. Molecular docking of phytochemicals against breast cancer can provide insights not only about these different mechaisms, but also about structural features required to improve inhibitory activities. Therefore, this study has focused on the computational analysis of selected phytochemicals that affect the transforming growth factor receptor (TGFBR) (1KSQ) and estrogen receptor (ER-α) (2IOG). Blind docking was performed and the binding free energies and Inhibition constants (Ki) were calculated. Higher binding free energies have shown for (+)-catechin and ellagic acid-4-O-xylopyranoside with TGFBR (-7.17 kcal/mol and - 7.38 kcal/mol respectively) and (+)-catechin, ellagic acid and ellagic acid-4-O-xylopyranoside with ER- α receptor (-7.84 kcal/mol, -7.26 kcal/mol and -8.82 kcal/mol respectively). Quercitrin has observed moderate binding free energy for both TGFBR (-6.58 kcal/mol) and ER-α receptor (-6.68 kcal/mol). Other phytochemicals like citric acid, gallic acid, and vanillic acid have observed relatively low binding free energies for both receptors. The binding affinities of pomegranate phytochemicals were compared with reference binding ligands (TGF-β for TGFBR and Estradiol for ER-α receptor) and present anticancer drug tamoxifen. According to the results, Ellagic acid-4-O-xylopyranoside has a lower inhibition constant than the other phytochemicals and it has higher inhibition for receptor-ligand complex. Therefore, it can be suggested that pomegranate contains an anti-breast cancer effect and the most effective phytochemical is Ellagic acid-4-O-xylopyranoside. Ellagic acid-4-O-xylopyranoside has shown greater binding affinity and lower inhibition constant for both receptors than the ellagic acid. Therefore, formation of derivatives of pomegranate phytochemicals can be more effective than the natural source. This study reveals that several pomegranate phytochemicals have been shown positive effects on cancer therapy. These findings will be further confirmed through molecular dynamics (MD) simulation studies.