Kinetic and Thermodynamic Study of Tolfenamic acid Interaction with Tau Protein Using Molecular Docking and Surface Plasmon Resonance

Abstract

Introduction: Alzheimer's Disease (AD) is a progressive neurodegenerative disease. In Alzheimer's patients, tau protein is phosphorylated due to genetic or environmental factors and accumulates inside the cell and forms tangles that interfere with cell function. Tolfenamic acid is a non-steroidal anti-inflammatory drug (NSAID) with a chemical structure similar to mefenamic acid. Tolfenamic acid can disrupt the pathological processes related to AD and be considered in AD patients. Therefore, we investigate the interaction between tolfenamic acid and tau protein from the perspective of kinetic, thermodynamic and molecular docking.Objective: In this research project, the kinetics and thermodynamics of the tolfenamic acid interaction with tau protein were successfully investigated using surface plasmon resonance and molecular docking methods.Materials and methods: After purifying and determining the concentration of tau protein, self-assembled monolayers of MUA was formed on Au chip surface. Then, carboxyl functional groups were activated using EDC/NHS solution and tau protein was immobilized on the modified chip surfaceThe non-specific active sites on the chip surface were blocked applying ethanolamine solution. Kinetic and thermodynamic studies were carried out using surface plasmon resonance device. Molecular docking was performed to investigate the interaction between tolfenamic acid and tau protein using AutoDock software.Results: The results of the studies showed that the dissociation equilibrium constant of the interaction of different concentrations of tolfenamic acid and tau increases while temperature increases and the stability of the resulting complex decreases.Conclusion: Enthalpy and entropy changes showed that hydrogen bond and vanderwaal force are the main force involved in the interaction between tau protein and tolfenamic acid and the reaction was exothermic and spontaneous.