Synthesis, Characterization, Antioxidant Activity of β-diketonates, and Effects of Coordination to Copper(II) ion on Their Activity: DNA, BSA Interactions and Molecular Docking Study

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Author(s): Nenad Joksimović, Jelena Petronijević, Nenad Janković, Marijana Kosanić, Dušan Milivojević, Milan Vraneš, Aleksandar Tot, Zorica Bugarčić*

Journal Name: Medicinal Chemistry

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Background: In order to make some progress in discovering the more effective way to eliminate ROS which cause the oxidative stress in organism in humans and bearing in mind the fact that ethyl-2-hydroxy-4-aryl(alkyl)-4-oxo-2-butenoates (β-diketonates) belong to a class of biologically active compounds, series of β-diketonates were synthesized, characterized, and tested to evaluate there antioxidant activity. Further, to investigate how coordination to copper(II) ion affects the activity of β-diketonates, appropriate complexes were synthesized and characterized.

Methods: All complexes were characterized by UV-Vis, IR, and EPR spectroscopy, MS spectrometry, and elemental analysis. Fluorescence spectroscopic method was used for investigations of the interactions between biomacromolecules (DNA or BSA) and compound 2E. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and compound 2E.

Results: Scavenging activity on DPPH radical revealed that compounds 2A, 2B, and 2E possess largest free radical scavenging, comparable to standard while results of superoxide anion scavenging activities of tested samples showed that maximum scavenging activity (IC50=168.92 µg/mL) was found for 2E, very similar to standard ascorbic acid, followed by 2B and 2G. Results of the interactions between biomacromolecules and 2E indicated that 2E has the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ± 0.1) × 103 M-1], while Ka value obtained via titration of BSA with 2E [Ka = (4.2 ± 0.2) × 105 M-1], support the fact that the significant amount of the drug could be transported and distributed through the cells.

Conclusions: All β-diketonates exhibited better scavenging activities than their corresponding copper complexes. Among all tested compounds, 2E gave the highest reducing power, even higher than standard ascorbic acid, while reducing power for compounds 2A and 2B was also good but lower than standard. DNA and BSA binding study for 2E showed that this compound has potential to be used as medicament.

Keywords: β-diketonates, antioxidant activity, copper complexes, DNA binding study, BSA binding study, molecular docking.

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(E-pub Ahead of Print)
DOI: 10.2174/1573406415666191024102520
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