Computational investigation of the antioxidant activity of sesamol and its ortho-amino derivatives in polar and nonpolar environments: Quantum chemical, molecular docking and drug likeness studies

Abstract

The natural sesamol, present in the seeds and oil of sesame, has attracted considerable interest for its powerful antioxidant properties. Its ability to neutralise free radicals and to inhibit lipid peroxidation highlight its potential as a therapeutic agent to reduce the oxidative stress. This explains the beneficial effects of sesamol as an effective protector against the damaging effects of reactive oxygen species (ROS). The antioxidant activity of sesamol and its ortho- mono- and di-substituted amino (R= NH2, NHMe and NHCN) derivatives has been investigated at the SMD//M06-2X/6-311+G(d,p) computational level. The calculations have been performed in the gas phase and in nonpolar (toluene) and polar (ethanol and water) solvents. The main mechanisms, namely, HAT, SPLET and SET-PT have been thoroughly investigated and analysed. The obtained results put in evidence that HAT and SPLET are the thermodynamically favoured mechanisms in non-polar and polar media respectively, while SET-PT is found to be a disfavoured mechanism in all media. The obtained results also show that di-substitution with strong electron-donating groups in the ortho- position leads to significant increase in their antioxidant activity compared to the reference molecule (sesamol). The antioxidant activity of the sesamol derivatives has also been evaluated by molecular docking to explore the possible interactions of each compound with the Xanthine Oxidase (XO) enzyme which is responsible for ROS generation and the obtained results show that these derivatives exhibit high binding affinities to the active site of the XO enzyme. Finally, the studied compounds satisfy both Lipinski and Veber drug likeness properties and could be considered as good radical scavengers.