An Integrated DFT and Molecular Simulation Study of 1,3,5‐Trihydroxybenzene (Phloroglucinol) for the Treatment of Breast Cancer

Abstract

In this study, the structure of 1,3,5‐trihydroxybenzene (135THB) was investigated using powder X‐ray diffraction and compared with simulated geometry. Its optimized molecular structure was analyzed for vibrational modes, electronic transitions, and interactions with breast cancer target proteins. Theoretical IR and UV–visible spectra were calculated and correlated with experimental data. Quantum chemical parameters, including reactive sites, atomic charges, and frontier molecular orbitals, were examined using density functional theory (DFT). Topological analysis and Hirshfeld surface mapping provided insights into molecular bonding and intermolecular interactions. Molecular docking with six breast cancer‐related proteins demonstrated favorable binding affinities, with the strongest interaction observed with AKT1 (−7.1 kcal/mol). This complex was further validated through a 100‐ns molecular dynamics simulation. ADMET and pharmacokinetic evaluations indicated that 135THB possesses good drug‐likeness and bioavailability. Overall, this work combines experimental spectroscopy, DFT calculations, multitarget docking, and molecular dynamics simulation, proposing 135THB as a promising candidate for future in vitro and in vivo anticancer studies.