A detailed insight into the interaction of memantine with bovine serum albumin: A spectroscopic and computational approach

摘要

Memantine is an NMDA receptor antagonist used to treat Alzheimer's disease. Detailed insight about the interaction between memantine and bovine serum albumin (BSA) was obtained through multi spectroscopic techniques and in silico analysis. UV-visible, steady-state fluorescence spectra, and resonance light scattering (RLS) studies showed the complex formation between memantine and BSA. The binding constant for the BSA-memantine complex was found to be in the order of 10(3) M-1. The local structural changes in BSA induced by memantine were detected by synchronous fluorescence spectroscopy (SFS), three-dimensional fluorescence and circular dichroism. The study of NaCl effect, as well as molecular docking, revealed the existence of electrostatic interaction in the complex formation. Binding constant was calculated in the presence of metal ions and their different combinations. Site marker fractional occupancy indicated that memantine binds to site IB of BSA. Additionally, the CD-based thermal unfolding profile showed that memantine has stabilizing effects on BSA. Molecular dynamics simulations further provided information on the stability and the forces involved in the binding of memantine with BSA. (C) 2020 Elsevier B.V. All rights reserved.