Investigating the potential of novel antioxidant flavonoids: a comprehensive study of drug-likeness, molecular docking, pharmacokinetics, and DFT analysis

Abstract Background Oxidative stress, triggered by an imbalance between reactive free radicals and the body’s antioxidant defenses, is linked to numerous health disorders including neurodegenerative ailments, cancer, and cardiovascular diseases. This study evaluates twenty-nine novel antioxidant flavonoids for their potential as therapeutic agents, focusing on drug-likeness, molecular interactions, pharmacokinetics, and electronic properties. Results Using SwissADME for drug-likeness analysis, all selected flavonoids met essential criteria. Molecular docking studies with the Keap1 protein identified Compounds 1, 13, and 15 as top performers, achieving MolDock scores of − 110.910, − 110.941, and − 117.329 kcal/mol, respectively, which indicate strong binding affinities. These compounds demonstrated significant interactions with key residues such as ARG-330 and GLU-250, whereas Ascorbic acid and Trolox showed lower scores of − 77.366 and − 101.037 kcal/mol, respectively. Pharmacokinetic predictions suggested high gastrointestinal absorption and blood–brain barrier permeability for the top flavonoids, with bioavailability scores of 0.55, compared to 0.56 for Ascorbic acid and 0.55 for Trolox. In the DFT assessment, HOMO–LUMO energy gaps were found to be 4.460 eV for Compound 1, 4.530 eV for Compound 13, and 4.520 eV for Compound 15, reflecting strong antioxidant activity. Additionally, electrophilicity indices ranged from − 3.993 to − 4.072, indicating significant electron-donating potential. QSAR analysis highlighted differences in dipole moments, hydrophobicities, and polar surface areas among the compounds, suggesting varied therapeutic potential. Conclusions This study highlights the promising potential of novel flavonoids as effective antioxidant agents. Evaluations of their drug-likeness, molecular interactions, and pharmacokinetic properties indicate a favorable profile for therapeutic applications. High binding affinities in molecular docking with the Keap1 protein suggest these flavonoids can modulate oxidative stress pathways, offering protection against various health disorders. Pharmacokinetic predictions show high gastrointestinal absorption and blood–brain barrier permeability, ensuring these compounds reach their target sites effectively. The use of advanced computational methods, such as DFT and QSAR analysis, enhances understanding of their properties and mechanisms. Overall, these findings support the development of effective antioxidant therapies for oxidative stress-related conditions.