In silico design of some potent antioxidant compounds using 2D-QSAR, molecular docking and ADMET studies

Background Oxidative stress caused by free radicals plays a major role in the development of ageing and several degenerative disorders, including cancer, cardiovascular diseases, diabetes, and Alzheimer’s disease. Therefore, the discovery of potent antioxidant agents remains an important research focus. This study aimed to design new antioxidant compounds based on neoflavonoid derivatives employing a ligand-based approach involving QSAR analysis, molecular docking, and ADMET prediction. Methods A QSAR model was developed using twenty-four neoflavonoids derivatives with the aid of Material Studio v8.0. Applicability domain and virtual screening were utilized to identify a suitable template compound, which was subsequently modified to design new potent compounds. Molecular docking was performed against Cu/Zn superoxide dismutase (PDB ID: 1HL5) using PyRx software. SwissADME and AdmetSAR servers were used to predict the drug-likeness and pharmacokinetic properties. Results Among the four generated QSAR models, model four was selected as the best model based on its statistical parameters (R 2 ext = 0.7810, R 2 trn = 0.9788, R 2 adj = 0.9723, Q 2 LOO = 0.9584, and cR²p = 0.6603). The designed compounds exhibited improved predicted antioxidant activities (pIC 50 = 4.97–5.61), compared with the template and ascorbic acid (pIC 50 = 4.43). Docking results revealed compounds 2, 4, and 3 as having notable docking scores of −7.7 kcal/mol, −7.4 kcal/mol, and −7.2 kcal/mol respectively. Furthermore, the ADMET results revealed favorable drug-likeness, good intestinal absorption, and potency for wet-lab production. Conclusions The designed neoflavonoid derivatives may serve as promising antioxidant agents subject to further in vitro and in vivo experiments.