Molecular Docking and ADMET Studies to Investigate Antioxidant Potency of New Amides of Piper retrofractum Vahl. by Targeting Keap1 Inhibitor Enung Siti Nurhidayah(a*), Darimiyya Hidayati(a), Risqina Amily Habiba(a), Syafira Maulidya(a)
a) Department of Agroindustrial Technology, Faculty of Agriculture, Universitas Trunojoyo Madura, Jl. Raya Telang, Kamal, Bangkalan, East Java, Indonesia
Abstract
Air pollution can cause increasing free radicals in the body. Antioxidants are important in maintaining the balance of free radicals in the body. Piper retrofractum Vahl is a traditional medicinal herb from Indonesia. This study investigates the possible interactions between new amides of piper recrofractum and Keap1 inhibitor, 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 van der Waals interaction and hydrogen bonds, including hydrogen bond distances. Finally, ADMET (adsorption, desorption, metabolism, excretion, toxicity) predictions and drug-likeness properties were performed on the investigated compound. Our study indicates that new amides from piper recrofractum may behave as potential natural antioxidant agents by targeting the Keap1 inhibitor.
