Thiourea Derivatives as Estrogen Receptor Alpha Inhibitors for Breast Cancer Therapy: An In Silico Evaluation with ADMET Prediction and Molecular Docking

Abstract

Breast cancer remains a significant public health challenge, necessitating the discovery of novel therapeutic agents. This study explores the potential of thiourea derivatives, specifically HU, HTMX, and BMPTU compounds, as estrogen receptor alpha (ERα) inhibitors using in silico approaches. Drug-likeness was assessed using Lipinski's Ro5, confirming good oral bioavailability for all compounds. ADMET analysis indicated favorable pharmacokinetic properties, with most derivatives demonstrating good intestinal solubility, minimal risks for metabolic interactions, and acceptable safety profiles, although BMPTU2 exhibited potential hepatotoxicity. Molecular docking studies revealed strong binding affinities for BMPTU derivatives, particularly BMPTU2, BMPTU3, and BMPTU4, which formed multiple hydrogen bonds and steric interactions with key ERα residues. These interactions suggest that BMPTU derivatives could function as ERα modulators, with further in silico and experimental validations needed to confirm their roles. Overall, the findings highlight BMPTU derivatives, especially BMPTU2, BMPTU3, and BMPTU4, as promising lead compounds for developing new breast cancer therapies targeting ERα. Further optimization and validation of these compounds are warranted to elucidate their therapeutic potential fully.