Identification of Some Bioactive Compounds from Camellia sinensis as Possible Inhibitors of human epidermal growth factor receptor 2 (HER2): A Structure-Based Drug Design for Breast Cancer Treatment.

Abstract

Background: Overexpression of HER2 has been related to a variety of malignancies, including breast cancer, and its inhibition has been established as an effective strategy for treating HER2-positive breast cancer. Because of its capacity to block carcinogenesis and reduce the proliferation of breast cancer cells, Camellia sinensis has been proven to be a source of anticancer agents. Methods: In this study, the phytochemical library of Camellia sinensis was screened for inhibitory potentials against HER2 using molecular docking, pharmacophore modelling, ADMET studies, and molecular dynamic (MD) simulation. Results: Gallocatechin, tricetinidin, SCHEMBL1950917, camellianin B, myricetin 3-glucoside, myricetin, camelliaside A, tricetin, faralateroside, and quercetin are the top-scoring compounds, with docking scores ranging from -9.327 kcal/mol to -8.147 kcal/mol. The selected compounds occupied the defined binding site and interacted with the same amino acid residues as the reference compound(03Q). The identified phytochemicals produced hydrophobic contacts with target amino acid residues of the HER2 ATP binding region in addition to one or more hydrogen bond interactions. Gallocatechin, possess favorable ADME properties and appeared to be the safest of all the chemicals, with an LD50 of 10,000 mg/kg, toxicity class 6, and no inclination toward any of the toxicity checkpoints. In the MD simulation, the gallocatechin-HER2 complex showed good stability, with GLN 799 and THR 862 retaining hydrogen bonds for 99% and 97% of the simulation, respectively. Conclusion: The HER2-inhibiting potentials and favorable ADMET properties demonstrated by these compounds, especially gallocatechin, make them suitable for further experimental studies and development into drugs against HER2-positive breast cancer.