Voltammetric quantification, spectroscopic, and DFT studies on the binding of the antineoplastic drug Azacitidine with DNA.

Autor: Şenel P; Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, Maslak, Istanbul 34469, Turkey., Agar S; Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, Maslak, Istanbul 34469, Turkey., Yurtsever M; Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, Maslak, Istanbul 34469, Turkey. Electronic address: mine@itu.edu.tr., Gölcü A; Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, Maslak, Istanbul 34469, Turkey. Electronic address: aysgolcu@itu.edu.tr.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Jan 05; Vol. 237, pp. 115746. Date of Electronic Publication: 2023 Oct 02.
DOI: 10.1016/j.jpba.2023.115746
Abstrakt: In this study, experimental studies were carried out to explore the action mechanism of the anti-cancer drug Azacitidine on the double-stranded DNA (dsDNA). The drug binding constant (K b ) was found to be 4.13 ± 0.23 × 10 5 M -1 using voltammetric measurements and 1.67 ± 0.24 × 10 5 M -1 using the fluorescence spectroscopy. Both values are close to the values of 2.04 ± 0.30 × 10 5 M -1 for deoxyguanosine (dGuO) and 1.23 ± 0.30 × 10 5 M -1 for deoxyadenosine (dAdo). In the displacement studies, the ethidium bromide, strong DNA intercalator, was replaced by the Azacitidine, hence caused a decrease on the fluorescence emission intensity. In thermal denaturation studies, the increase of 8.60 °C in the melting temperature upon introduction of the Azacitidine into the dsDNA solution cleary indicated intercalation binding mode of the drug. The experimental and theoretical IR spectra of Azacitidine, dsDNA and their H-bonded complex were confirmed the Azacitidine's intercalation ability to induce cytotoxicity. We also developed a method for the detection of Azacitidine at low concentrations using the differential pulse voltammetry (DPV). The peak current decreases in the oxidation signals of the deoxyguanosine obtained voltammetrically upon the interaction of Azacitidine and dsDNA allowed a sensitive determination of Azacitidine in pH 4.80 acetate buffer. A linear dependence of the deoxyguanosine oxidation signals was observed within the range of 2-20 µM Azacitidine, with a limit of detection (LOD) 0.62 µM.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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