فهرست نشریات علمی دسترسی آزاد ایران

Oxidative stress plays a critical role in various pathologies, necessitating the development of potent Keap1 inhibitors. This study addresses the research gap by employing a comprehensive computational approach to identify novel Keap1 inhibitors from a library of 61 antioxidant compounds obtained from PubChem. Molecular docking simulations, ADMET property prediction, Density Functional Theory (DFT) calculations, and QSAR analysis were utilized. Three compounds (8, 33, and 58) were selected based on their significantly superior MolDock scores (-138.914, -169.902, and -134.798 kcal/mol, respectively) compared to Ascorbic acid (-77.366 kcal/mol), indicating strong binding affinities. These compounds exhibited high stability through hydrogen bonds and hydrophobic interactions with key Keap1 residues. ADMET analyses confirmed favorable drug-like properties and safety profiles, suggesting potential for combination therapy. DFT calculations provided insights into their electronic properties, including HOMO, LUMO, and energy gap values, while molecular electrostatic potential maps illustrated charge density distributions relevant to biological activity. QSAR analysis highlighted differences in physicochemical properties, indicating varied therapeutic potential. Overall, these findings support the development of effective antioxidant therapies for oxidative stress-related conditions.