Acridine derivatives inhibit lysozyme aggregation.
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.
Gazova
Zuzana
Z
Department of Biophysics, Institute of Experimental Physics, Watsonova 47, 040 01, Kosice, Slovakia. gazova@saske.sk
Bellova
Andrea
A
Daxnerova
Zuzana
Z
Imrich
Jan
J
Kristian
Pavol
P
Tomascikova
Jana
J
Bagelova
Jaroslava
J
Fedunova
Diana
D
Antalik
Marian
M
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
D000166:Acridines; D000682:Amyloid; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D013844:Thiazoles; C484811:bis-acridine; C009462:thioflavin T; D009113:Muramidase