Computational Exploration into the Antioxidant Activity of Some Phenolic Compounds Isolated from Moringa Oleifera Using Molecular Docking Studies, DFT Studies, Pharmacokinetics and Determination of Antioxidant Properties

Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of oxygen reactive species (ROS) in cells and tissues. Antioxidants are known to play an important role in preventing diseases caused by oxidative stress such as cancer, heart disease, diabetes, stroke, rheumatoid arthritis, Alzheimer's disease, ageing, and cataracts. Natural antioxidants are considered safer and healthier compared with their synthetic origin. Most of the naturally available ones are phenolic compounds. Antioxidants having phenolic groups are the most widely used ones. Even while the hunt for antioxidant medications from plants has been the subject of numerous wet lab investigations, the high costs, high failure rates and lengthy development times have made this a challenge. Therefore, there is a need to propose a more effective approach to curb the aforementioned challenges. This research study pursues to propose a promising antioxidant drug candidate in an environment free of the challenges associated with the wet lab approach as mentioned earlier. The research findings identify four potential antioxidant candidates through molecular docking studies of some phenolic compounds isolated from Moringa oleifera. Geometric optimization performed using Spartan 14 software on the data collected from literatures and crystal structure of the protein enzyme retrieved from protein data bank (PDB ID:3WGX). The molecular docking simulation performed using molegro virtual docker provide four best hit compounds with higher docking scores than Ascorbic acid, the standard drug. The four best hit compounds are compound 9,4,10 and 8 with docking scores -138.04 kcal.mol-1, -123.399 kcal.mol-1, -117.287 kcal.mol-1 and -116.956 kcal.mol-1 respectively while the standard drug had a moldock score of -81.433 kcal.mol-1.Further screening of their physiochemical and ADMET properties using Lipinski, Ghose and Veber rules yield four best compounds with remarkable pharmacokinetics and non-toxicity. DFT calculations were also performed on the four lead compounds to investigate their quantum chemical parameters (Homo Lumo energy band gap, hardness, softness, electronegativity, chemical potential and elecrophilicity) which helps in understanding their physical and chemical properties, and the results revealed their higher reactivity than the standard drug. Due to the high efficiency of the computational approach, this research was able to probe into the radical scavenging potency of the phenolic groups present in the respective lead compounds and the results showed they have higher potency compared to the standard drug. Thus, the research concludes that these ligands can be further modelled into a more effective antioxidant in comparison to ascorbic acid, the standard drug.