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Acridine derivatives inhibit lysozyme aggregation

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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.

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Acknowledgments

This work was supported by the research grants from the Slovak Grant Agency VEGA No. 7055, 2471, 6167, 0056 and VVGS grant PF8/2007/CH. Dr. M. Vilkova, Dr. S. Hamulakova and Dr. E. Balentova are thanked for kind providing of selected tested compounds.

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Authors and Affiliations

  1. Department of Biophysics, Institute of Experimental Physics, Watsonova 47, 040 01, Kosice, Slovakia

    Zuzana Gazova, Jaroslava Bagelova, Diana Fedunova & Marian Antalik

  2. Faculty of Sciences, P. J. Safarik University, Moyzesova 11, 041 54, Kosice, Slovakia

    Andrea Bellova, Zuzana Daxnerova, Jan Imrich, Pavol Kristian, Jana Tomascikova & Marian Antalik

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  1. Zuzana Gazova
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  2. Andrea Bellova
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Correspondence to Zuzana Gazova.

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Regional Biophysics Conference of the National Biophysical Societies of Austria, Croatia, Hungary, Italy, Serbia, and Slovenia.

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Gazova, Z., Bellova, A., Daxnerova, Z. et al. Acridine derivatives inhibit lysozyme aggregation. Eur Biophys J 37, 1261–1270 (2008). https://doi.org/10.1007/s00249-008-0313-0

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