title: Acridine derivatives inhibit lysozyme aggregation.
abstract: We have screened a library of structurally distinct acridine derivatives (19 compounds) for their ability to inhibit lysozyme amyloid aggregation in vitro. Studied acridines were divided into three structurally different groups depending on the molecule planarity and type of the side chain-planar acridines, spiroacridines and tetrahydroacridines. Thioflavine T fluorescence assay and transmission electron microscopy were used for monitoring the inhibiting activity of acridines. We have found that both the structure of the acridine side chains and molecule planarity influence their antiamyloidogenic activity. The planar acridines inhibited lysozyme aggregation effectively. Spiroacridines and tetrahydroacridines had no significant effect on the prevention of lysozyme fibrillization, probably resulting from the presence of the heterocyclic 5-membered ring and non-planarity of molecule. Moreover, in the presence of some tetrahydroacridines the enhanced extent of aggregation was detected. We identified the most active acridine derivates from studied compound library characterized by low micromolar IC50 values, which indicate their possible application for therapeutic purpose.
authors.affiliation: Department of Biophysics, Institute of Experimental Physics, Watsonova 47, 040 01, Kosice, Slovakia. gazova@saske.sk
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Gazova
authors.forename: Andrea
authors.initials: A
authors.lastname: Bellova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Daxnerova
authors.forename: Jan
authors.initials: J
authors.lastname: Imrich
authors.forename: Pavol
authors.initials: P
authors.lastname: Kristian
authors.forename: Jana
authors.initials: J
authors.lastname: Tomascikova
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Bagelova
authors.forename: Diana
authors.initials: D
authors.lastname: Fedunova
authors.forename: Marian
authors.initials: M
authors.lastname: Antalik
mesh_terms: D000166:Acridines / Q000737:chemistry* / Q000494:pharmacology*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008970:Molecular Weight; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
chemical_list: D000166:Acridines; D000682:Amyloid; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D013844:Thiazoles; C484811:bis-acridine; C009462:thioflavin T; D009113:Muramidase