Exploring zingerone 2-thiohydantoins as anticancer agents against breast adenocarcinoma: Cytotoxicity, HSA and DNA binding, molecular docking and ADMET prediction

This study investigates a series of zingerone 2-thiohydantoins for anticancer activity towards human breast adenocarcinoma and explores possible mechanisms of anticancer action. Cytotoxicity was tested on highly invasive triple negative breast cancer MDA-MB-231 cells and healthy MRC-5 cells. The most active compound 2e exerted a significant cytotoxic effect on breast cancer cells, while exhibiting no measurable toxicity on healthy cells. Fluorescence measurements of interactions with human serum albumin, combined with molecular docking, showed strong binding and transport capabilities, suggesting good bioavailability. Fluorescence and hydrodynamic measurements with DNA displayed lower binding affinity, suggesting that protein targets are responsible for anticancer action. Thorough molecular docking screening on 36 possible breast adenocarcinoma protein targets was performed and results suggest competitive inhibition of DNA methyltransferase 1 as the mechanism of anticancer action. ADMET analysis predicted favorable physicochemical and pharmacokinetic properties.