In silico evaluation of natural nothoapiol derivatives for antioxidant activity

Medicinal plants have long been recognized as valuable sources of natural compounds with significant therapeutic potential. They contain a wide variety of bioactive secondary metabolites, such as alkaloids and phenolic compounds, many of which serve as lead molecules in modern drug discovery. Owing to their structural diversity and broad spectrum of biological activities, these natural products represent an essential resource for developing novel drugs with enhanced efficacy and reduced side effects. In particular, numerous plant-derived compounds have demonstrated promising inhibitory effects against key enzymes, including xanthine oxidase (XO). XO is a crucial enzyme in purine metabolism, catalyzing the oxidation of hypoxanthine to xanthine and subsequently to uric acid.

In this study, three nothoapiol derivatives derived from essential oils were extracted from the medicinal plant Petroselinum sativum by V. Samet et al. These compounds exhibited excellent in vitro antioxidant activity. To further elucidate their mechanism of inhibition and evaluate their potential as XO inhibitors, an in silico molecular docking study was performed. Docking simulations were carried out using Schrödinger Suites 2023, with Glide employing the extra-precision (XP) docking protocol.

The docking results revealed that the nothoapiol derivatives exhibited strong binding affinities, with docking scores comparable to that of quercetin, a well-known standard XO inhibitor. Detailed interaction analysis demonstrated the formation of hydrogen bonds, hydrophobic interactions, and π–π stacking with key active site residues such as Ser876, Lys771, Phe1013, and Glu802, which are critical for XO catalytic activity. These findings suggest that the structural features of the nothoapiol derivatives particularly the presence of hydroxyl and methoxy substituents play a crucial role in enhancing binding stability and specificity.