Insight into the intercalation of N-substituted acridine-9-amines into DNA based on spectroscopic and calorimetric analysis.

Autor: Żamojć K; Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland. Electronic address: krzysztof.zamojc@ug.edu.pl., Milaș D; Faculty of Chemistry, Biology, Geography, West University of Timișoara, Strada Johann Heinrich Pestalozzi 16, Timișoara, Romania., Grabowska O; Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland., Wyrzykowski D; Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland., Mańkowska M; Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland., Krzymiński K; Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2024 Dec 16; Vol. 1869 (2), pp. 130741. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1016/j.bbagen.2024.130741
Abstrakt: The study delves into the binding properties of acridine-9-amine and its selected, mainly N-substituted derivatives (A9As), with calf thymus deoxyribonucleic acid (CT-DNA). This investigation, conducted using UV-Vis spectrophotometry, steady-state fluorescence spectroscopy and isothermal titration calorimetry, provides insights into the relationship between their structure and activity. The absorption spectra of the A9As exhibited a slight red shift and significant hypochromic effects, while the fluorescence emission intensities decreased in the presence of CT-DNA. These results suggest that all fluorescent substrates intercalate into the double helix of native DNA to varying degrees. The binding constants for the A9As/CT-DNA complexes (log(K A ) were determined using various techniques in the range from 2.59 to 5.50). The thermodynamic parameters of A9As binding to DNA were obtained from ITC measurements (ΔG from - 7.51 to - 6.75 kcal·mol -1 , ΔH from - 11.58 to - 3.83 kcal·mol -1 , and TΔS from - 4.83 to 3.68 kcal·mol -1 ) and indicated that the formation of all the investigated A9As-DNA complexes is an enthalpy-driven process. The study also discusses the influence of the emitters' structure and electronic properties of substituents on intercalation efficiency. This knowledge serves as a guide for further research and offers directions for functionalising new acridines as potential reagents. It also provides the latest information on the ability of intercalation to DNA, which can be instrumental in studies on the mechanism of binding small aromatic molecules to DNA and can potentially contribute to new anticancer drug designs.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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