The interactions of monomeric acridines and unsymmetrical bisacridines (UAs) with DNA duplexes: an insight provided by NMR and MD studies - Publication - Bridge of Knowledge

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The interactions of monomeric acridines and unsymmetrical bisacridines (UAs) with DNA duplexes: an insight provided by NMR and MD studies

Abstract

Members of a novel class of anticancer compounds, exhibiting high antitumor activity, i.e. the unsymmetrical bisacridines (UAs), consist of two heteroaromatic ring systems. One of the ring systems is an imidazoacridinone moiety, with the skeleton identical to the structural base of Symadex. The second one is a 1-nitroacridine moiety, hence it may be regarded as Nitracrine’s structural basis. These monoacridine units are connected by an aminoalkyl linker, which vary in structure. In theory, these unsymmetrical dimers should act as double-stranded DNA (dsDNA) bis-intercalators, since the monomeric units constituting the UAs were previously reported to exhibit an intercalating mode of binding into dsDNA. On the contrary, our earlier, preliminary studies have suggested that specific and/or structurally well-defined binding of UAs into DNA duplexes might not be the case. In this contribution, we have revisited and carefully examined the dsDNA-binding properties of monoacridines C-1305, C-1311 (Symadex), C-283 (Ledakrin/Nitracrine) and C-1748, as well as bisacridines C-2028, C-2041, C-2045 and C-2053 using advanced NMR techniques, aided by molecular modelling calculations and the analysis of UV–VIS spectra, decomposed by chemometric techniques. These studies allowed us to explain, why the properties of UAs are not a simple sum of the features exhibited by the acridine monomers.

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DOI:
Digital Object Identifier (open in new tab) 10.1038/s41598-023-30587-y
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Category:
Articles
Type:
artykuły w czasopismach
Published in:
Scientific Reports no. 13,
ISSN: 2045-2322
Language:
English
Publication year:
2023
Bibliographic description:
Laskowski T., Kosno M., Andrałojć W., Frąckowiak J., Borzyszkowska-Bukowska J., Szczeblewski P., Radoń N., Świerżewska M., Woźny A., Paluszkiewicz E., Mazerska Z.: The interactions of monomeric acridines and unsymmetrical bisacridines (UAs) with DNA duplexes: an insight provided by NMR and MD studies// Scientific Reports -Vol. 13, (2023), s.3431-
DOI:
Digital Object Identifier (open in new tab) 10.1038/s41598-023-30587-y
Sources of funding:
  • IDUB
Verified by:
Gdańsk University of Technology

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