Lysozyme amyloid fibrillization in presence of tacrine/acridone-coumarin heterodimers
Journal
Colloids and Surfaces B: Biointerfaces
Journal Volume
166
Pages
108-118
Date Issued
2018
Author(s)
Abstract
Amyloid aggregates of proteins are one of the most abundant and important naturally occurring self-associated assemblies. Formation of poly/peptide amyloid aggregates is also associated with the widely spread diseases, so called amyloidosis, which include Alzheimer's disease, diabetes mellitus and lysozyme amyloidosis. These disorders are still incurable and novel therapeutical approaches are focused on using small molecules for inhibition of amyloid aggregation. We have observed effect of three structurally distinct groups of tacrine/acridone ¡V coumarin heterodimers on hen egg white (HEW) lysozyme fibrillization in vitro. The ability of heterodimers to interfere with lysozyme amyloid aggregation was examined using Thioflavin T fluorescence assay, atomic force microscopy and docking method. The obtained data suggest that inhibitory effect of heterodimers on lysozyme fibrillization depends on their composition. We have shown that tacrine-coumarin heterodimers with alkylenediamine linker are the most effective inhibitors of lysozyme fibrillization. The inhibitory activities were quantified through IC 50 values; the most potent heterodimers interfere with lysozyme aggregation in the scale of micromolar concentrations (19.2 £gM¡V105.4 £gM). The molecular docking showed that the modes of possible interactions involved in the binding are mainly hydrophobic interactions, hydrogen bonding and van der Waals interactions. Studied heterodimers had none or weak cytotoxic effect on human neuroblastoma cells. The obtained results can be helpful for the design and development of new therapeutics for amyloid-related diseases. ? 2018 Elsevier B.V.
Subjects
Acridone
Amyloid aggregation
Coumarin
Inhibitors
Lysozyme
Tacrine
SDGs
Other Subjects
Aggregates; Atomic force microscopy; Corrosion inhibitors; Cytotoxicity; Glycoproteins; Hydrogen bonds; Hydrophobicity; Neurodegenerative diseases; Van der Waals forces; Acridones; Amyloid-related disease; Coumarin; Hen egg white lysozyme; Hydrophobic interactions; Micromolar concentration; Tacrine; Van Der Waals interactions; Enzymes; acridone derivative; amyloid; coumarin; egg white; heterodimer; lysozyme; tacrine; amyloid; coumarin; coumarin derivative; lysozyme; tacrine; Article; atomic force microscopy; chemical phenomena; chemical reaction; controlled study; enzyme binding; fibrillization; fluorescence analysis; human; human cell; hydrogen bond; hydrophobicity; IC50; in vitro study; limit of quantitation; molecular docking; priority journal; protein aggregation; protein assembly; protein protein interaction; reaction analysis; van der Waals interaction; chemistry; metabolism; Amyloid; Coumarins; Humans; Microscopy, Atomic Force; Muramidase; Tacrine
Type
journal article