Structural, Theoretical and Molecular Docking Evaluation of 2-Methyl-1,4-naphthoquinone as Potential Anti-Breast Cancer Agent

Abstract

The DFT-B3LYP/6-311++G(d,p) method was employed to investigate the vibrational characteristics of 2-methyl-1,4-naphthoquinone (2MNQ), with results compared against FTIR and FT-Raman spectra recorded in the 3500–400 cm^–1 range. The optimized molecular geometry was validated through comparison with both theoretical predictions and experimental X-ray diffraction (XRD) data. Charge density distributions were analyzed to elucidate the energy gap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) and to construct the molecular electrostatic potential (MEP) map, offering insights into the potential biological activity of compound. Electronic absorption spectra were simulated using time-dependent density functional theory (TD-DFT) with the same basis set. Mulliken charge analysis highlighted significant electron delocalization, supporting the electronic reactivity of molecule. Moreover, the density of states (DOS) spectrum was examined to identify key molecular orbital contributions. Molecular docking studies revealed that 2MNQ exhibited the highest binding affinity with the breast cancer-related protein 1M17, showing a binding energy of –7.2 kcal/mol. ADMET predictions further assessed the drug-likeness and pharmacokinetic properties of the compound. These combined theoretical and experimental findings provide valuable insights into the molecular structure and potential pharmacological applications of 2MNQ.