In vitro antioxidant activity, QSAR, in silico toxicity prediction, molecular docking studies, and molecular dynamics of a series of N-ferrocenylmethylanilines as potent antioxidant agents

The superoxide anion radical scavenging activities of a series of twenty-eight ferrocenylmethylaniline derivatives were measured in an in vitro study followed by in silico studies which included quantitative structure-activity relationship (QSAR), toxicity prediction, molecular docking studies, and molecular dynamics simulations. Multilinear regression analysis was employed to establish a quantitative correlation between the scavenging activity of superoxide anion radicals and various structural properties. The QSAR model obtained underwent validation, demonstrating statistical significance with a squared fitting correlation coefficient (R2) of 0.934, an adjusted squared correlation coefficient (R2 adj) value of 0.849, and a cross-validation coefficient (Q2) value of 0.873. Additionally, the calculated Fisher ratio (F) value of 36.525 indicates the model's strong predictability. Toxicity perdition studies demonstrated that among the five most potent compounds, FMA27 and FMA12 were predicted to be non-toxic. The molecular Docking study revealed that compound FMA23 exhibited the least activity against the glutathione reductase enzyme, with the highest inhibitory concentration recorded at 4.16 x 10-6 M and the lowest docking scores observed at -7.34 kcal.mol-1. Interactions between the compound and the amino acid residues of glutathione reductase were primarily hydrophobic and It-cation in nature. Analysis of root mean square deviation (RMSD), radius of gyration (Rg), and root mean square fluctuation (RMSF), from molecular dynamics study, revealed stable fluctuations in protein backbone conformations, consistent compactness of the complex, and minimal fluctuations in most protein residues, respectively.