Structural Reactivity of Diimine‐Dioxime Molecules in Anticancer Research: Quantum Chemical Insights, Molecular Modeling and ADMET Studies

Abstract This study carried out quantum chemical calculations and molecular modeling studies of five diimine‐dioxime molecules (1–5). The optimized molecular geometries, HOMOs–LUMOs and molecular electrostatic potential (MEP) diagrams of the molecules were calculated at the DFT/B3LYP/6–311G(d,p) level of theory. The calculated global reactivity parameters revealed that the hardest and most stable molecule is 1 ( η = 1.897 eV), while the softest and most chemically reactive molecule is 2 ( S = 1.621 eV −1 ). All compounds in silico ADMET and drug‐likeness parameters were generally within acceptable limits and all compounds except 3 were considered to have good oral bioavailability. Molecular docking studies were also performed using VEGFR2 (PDB ID: 2XIR) and EGFR (PDB ID: 1M17) proteins to predict the potential anticancer properties of the molecules. All binding energies obtained in molecular docking studies were between −7.8 and −9.7 kcal/mol. The behavior of the 2–2XIR complex with the best binding energy value of −9.7 kcal/mol under physiological conditions was performed by molecular dynamics (MD) simulation for 100 ns. The RMSD, RMSF, SASA, Rg, and hydrogen bonding parameters obtained by MD simulation confirmed the conformational stability of the 2–2XIR complex. All the results indicated that molecule 2 has the potential to contribute to studies on discovering new anticancer agents.