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

Pelin Şenel, Soykan Agar, Mine Yurtsever*, Ayşegül Gölcü

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Özet

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 (Kb) was found to be 4.13 ± 0.23 × 105 M−1 using voltammetric measurements and 1.67 ± 0.24 × 105 M−1 using the fluorescence spectroscopy. Both values are close to the values of 2.04 ± 0.30 × 105 M−1 for deoxyguanosine (dGuO) and 1.23 ± 0.30 × 105 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.

Orijinal dilİngilizce
Makale numarası115746
DergiJournal of Pharmaceutical and Biomedical Analysis
Hacim237
DOI'lar
Yayın durumuYayınlandı - 5 Oca 2024

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© 2023

Finansman

This study was supported by a grant of Istanbul Technical University under TDK2020–42630 and TDK-2021–43464 project.The authors thank the support of the grant of Istanbul Technical University (Scientific Research Projects Unit) under TDK-2020–42630 and TDK-2021–43464. M.Y. acknowledges the computer time provided by the National High Performance Computing Center (UHEM) under grant number 5004452017. We also thank Dr. Bünyamin Karagoz (ITU, Chemistry Dep.) allowed us to carry out the fluorescence experiments in his laboratory. We would like to thank Deva Holding and especially Dr. Esen Bellur Atici (R&D Center, DEVA Holding A.S. Tekirdağ, 59510, Turkey) who helped us in obtaining Azacitidine and Vidaza 100 mg SC injection Suspension on request. The authors thank the support of the grant of Istanbul Technical University (Scientific Research Projects Unit) under TDK-2020–42630 and TDK-2021–43464. M.Y. acknowledges the computer time provided by the National High Performance Computing Center (UHEM) under grant number 5004452017 . We also thank Dr. Bünyamin Karagoz (ITU, Chemistry Dep.) allowed us to carry out the fluorescence experiments in his laboratory. We would like to thank Deva Holding and especially Dr. Esen Bellur Atici (R&D Center, DEVA Holding A.S., Tekirdağ, 59510, Turkey) who helped us in obtaining Azacitidine and Vidaza 100 mg SC injection Suspension on request. This study was supported by a grant of Istanbul Technical University under TDK2020–42630 and TDK-2021–43464 project.

FinansörlerFinansör numarası
Deva Holding59510
Ulusal Yüksek Başarımlı Hesaplama Merkezi, Istanbul Teknik Üniversitesi5004452017
Istanbul Teknik ÜniversitesiTDK-2020–42630, TDK-2021–43464
Sheikh Bahaei National High Performance Computing Center, Isfahan University of Technology

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