Exploring the inhibitory potentials of Momordica charantia bioactive compounds against Keap1-Kelch protein using computational approaches

• Published in: In silico pharmacology 2021-06, Vol.9 (1), p.39-39, Article 39
• Main Authors: Adelusi, Temitope Isaac, Abdul-Hammed, Misbaudeen, Idris, Mukhtar Oluwaseun, Kehinde, Oyedele Qudus, Boyenle, Ibrahim Damilare, Divine, Ukachi Chiamaka, Adedotun, Ibrahim Olaide, Folorunsho, Ajayi Ayodeji, Kolawole, Oladipo Elijah
• Format: Article
• Language: English
• Subjects: Amino acids; Antioxidants; Binding energy; Binding sites; Biological activity; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Catechin; Cellular and Medical Topics; Chlorogenic acid; Computational Science and Engineering; Domains; Gibbs free energy; Herbal medicine; Hydrogen bonds; Investigations; Ligands; Mathematical analysis; Medicinal Chemistry; Molecular docking; Molecular dynamics; Original Research; Oxidative stress; Pharmacology; Pharmacology/Toxicology; Physiological; Proteins
• ISSN: 2193-9616; 2193-9616
• DOI: 10.1007/s40203-021-00100-2

The search for Keap1 inhibitors as potential Nrf2 activator is a way of increasing the antioxidant status of the human cellular environ. In this research, we used in silico methods to investigate Keap1-kelch inhibitory potential of Momordica charantia’s bioactive compounds in order to predict their Nrf2 activating potential. ADMET profiling, physicochemical properties, molecular docking, molecular dynamics, and Molecular Mechanics-Poisson Boltzmann Surface Area (g_MMPBSA) free energy calculation studies were executed to drive home our aim. Out of all the bioactive compounds of Momordica charantia , catechin (CAT) and chlorogenic acid (CGA) were selected based on their ADMET profile, physicochemical properties, and molecular docking analysis. Molecular docking studies of CAT and CGA to Keap1 kelch domain showed that they have − 9.2 kJ/mol and − 9.1 kJ/mol binding energies respectively with CAT having four hydrogen bond interactions with Keap1 while CGA had three. Analysis after the 30 ns molecular dynamics simulation revealed that CAT and CGA were both stable, although with minimal conformational alterations at the kelch pocket of Keap1. Finally, MMPBSA calculation of the Gibbs free energy of each amino acid interaction with CAT and CGA revealed that CAT had a higher total binding energy than CGA. Therefore, the Keap1 inhibitory capacities and the molecular dynamic characters of CAT and CGA at the Kelch domain of Keap1 suggest a putative Nrf2 signaling activating prowess. Graphic abstract