Isolation, characterization and in silico docking studies of synergistic estrogen receptor a anticancer polyphenols from Syzygium alternifolium (Wt.) Walp.

Abstract

This study aims to isolate, characterize, and in silico evaluate of anticancer polyphenols from different parts of Syzygium alternifolium. The polyphenols were isolated by standard protocol and characterized using Fourier-transform infrared (FT-IR), High performance liquid chromatography - Photodiode array detector coupled with Electrospray ionization - mass spectrometry (MS/MS). The compounds were elucidated based on retention time and molecular ions (m/z) either by [M+H]+/[M-H]- with the comparison of standard phenols as well as ReSpect software tool. Furthermore, absorption, distribution, metabolism, and excretion (ADME)/toxicity properties of selected phenolic scaffolds were screened using OSIRIS and SwissADME programs, which incorporate toxicity risk assessments, pharmacokinetics, and rule of five principles. Molecular docking studies were carried out for selected toxicity filtered compounds against breast cancer estrogen receptor a (ERa) structure (protein data bank-ID: 1A52) through AutoDock scoring functions by PyRx virtual screening program. The obtained results showed two intensive peaks in each polyphenol fraction analyzed with FT-IR, confirms O-H/C-O stretch of the phenolic functional group. A total of 40 compounds were obtained, which categorized as 9 different classes. Among them, flavonol group represents more number of polyphenols. In silico studies suggest seven compounds have the possibility to use as future nontoxic inhibitors. Molecular docking studies with ERa revealed the lead molecules unequivocally interact with Leu346, Glu353, Leu391, Arg394, Gly521, Leu525 residues, and Phe404 formed atomic π-stacking with dihydrochromen-4-one ring of ligands as like estrodial, which stabilizes the receptor structure and complicated to generate a single mutation for drug resistance. Overall, these results significantly proposed that isolated phenolics could be served as potential ER mitigators for breast cancer therapy.