Molecular Modeling, ADME and Density Functional Theory Studies of Novel Acylhydrazone Derivatives Targeted Epidermal Growth Factor Receptor

Abstract

Targeting the epidermal growth factor receptor (EGFR) has emerged as a significant strategy in anticancer therapy. Nonetheless, adverse effects and resistance mechanisms often hinder the efficacy of medications that target EGFR. This work employed molecular modeling to investigate novel derivatives of 1,3,4-Oxidazole, aiming to develop more efficacious and less toxic agents for cancer therapy. The derivatives were subjected to docking and dynamics simulations inside the EGFR active site, facilitating the evaluation of their binding affinities. We assessed the electronic properties of the system, namely the energies of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs), via Density Functional Theory (DFT) computations, which yielded insights into their reactivity parameters. We utilized Root Mean Square Deviation (RMSD) analysis to evaluate the conformations of different ligands, offering essential structural dynamics insights for the design and development of medicines aimed at EGFR suppression. The results demonstrated that compounds (8, 4, 1, 3, 6) displayed superior binding characteristics with the active site of our target.