Background: An estimated 1 in 8 men may acquire prostate cancer at some point in their lives, making it one of the most common malignancies to affect men globally. The androgen receptor (AR), linked to controlling genes essential for cell survival and proliferation, is a major therapeutic target in prostate cancer. The 1E3G is vital to the development of the disease

Objective: This study aims to computationally investigate potential 1E3G receptor inhibitors for prostate cancer treatment. Using molecular docking, DFT analysis, and ADMET profiling, compounds such as Cianidanol and Gallocatechin are assessed for their binding characteristics and pharmacological interactions to identify promising therapeutic candidates for further development.

Materials and methods: Using a computational ligand-based method, the molecular chemical characteristics of 1E3G inhibition were determined. Potential inhibitors such as Cianidanol and Gallocatechin were investigated from Camellia sinensis (Theaceae) and Phyllanthus amarus (Euphorbiaceae). In this study, the DFT 6-31g(d,p) basis set, ADMET, and the Gaussian 16 software package were utilized to compute the physical, chemical, spectral, and thermodynamic properties of specific ligands. The interaction between ligands and proteins was examined with PyRx, Chimera 1.15. Molecular orbital studies were used to calculate the softness and binding characteristics whereas network pharmacology studies examined the interaction of protein and ligands. Additionally, pharmacokinetics was assessed using renowned web tools such as admetSAR, and ProTox-3.0 for predicting toxicity. Moreover, 100 nanoseconds molecular dynamics simulation analysis using Desmond to ensure the stability of these two compounds.

Results: Based on computational research, drug binding site evaluation, docking score, optimization, and molecular dynamic simulation results Cianidanol(Binding affinity -8.1) and Gallocatechin (Binding affinity -8.4)are the most selective 1E3G inhibitors.

Conclusion: These compounds are required to be studied further to develop a useful 1E3G inhibitor for the treatment of Prostate Cancer.