Molecular Docking and ADMET Studies to Investigate Antioxidant Potency of New Amides of Piper retrofractum Vahl by Targeting Keap1 Inhibitor

Abstract

Abstract Antioxidants are considered important in maintaining the balance of free radicals in the body due to exposure to air pollution. Piper retrofractum Vahl which is a traditional Indonesian medicinal herb which is said to have the characteristics of being an antioxidant in preventing free radicals in the body. Therefore, this research aims to investigate possible interactions between new amides of Piper retrofractum Vahl. and Keap1, one of the key proteins of the Keap1/Nrf2 pathway, the major system involved in redox regulation. Molecular docking study, using molecular mechanic calculations with Yasara to investigate binding energy and pkCSM to predict ADMET. Results this study showed that dipiperamides F has binding energy of 9.855 kcal/mol (closest to that of the crystallographic ligands), dipiperamides G (9.543 kcal/mol), piperodione (8.448 kcal/mol), (E)-N-cinnamoyl-2-methoxypiperidine (7.560 kcal/mol), (2E, 12E)-pipertride cadienamid (7.084 kcal/mol), N-isobutyl-(2E, 4E, 10Z)-hexadeca-2, 4, 10-trienamide (6.788 kcal/mol), (R)-1-(2-oxopyrrolidin-3-yl)-5, 6-dihydropyridin-2(1H)-one (6.524 kcal/mol), 2E, 14Z)-N-isobutyleicosa-2, 14-dienamide (5.116 kcal/mol). Visualization of receptors-ligands complex showed data on hydrogen bonds and no-covalen interactions, including hydrogen bond distances. Finally, ADMET (Adsorption, Desorption, Metabolism, Excretion, Toxicity) predictions and drug-likeness properties were performed on the tested compound. Our study indicates that new amides from Piper retrofractum Vahl may behave as potential natural antioxidant agents by targeting the Keap1 inhibitor.