Small Molecule Interactions with Biomacromolecules: DNA Binding Interactions of a Manganese(III) Schiff Base Complex with Potential Anticancer Activities

Abstract

((E)-(2-((E)-2-hydroxy-3-methoxybenzylidene-amino)-ethylimino)methyl)-6-methoxyphenol), has been synthesized and characterized by single-crystal X-ray diffraction analysis. The interaction of 1•H 2 O with DNA was studied by monitoring the decrease in absorbance of the complex at λ = 324 nm with the increase in DNA concentration, providing an opportunity to determine the binding constant of the 1•H 2 O−ct-DNA complex as 5.63 × 10 3 M −1 . Similarly, fluorescence titration was carried out by adding ct-DNA gradually and monitoring the increase in emission intensity at 453 nm on excitation at λ ex = 324 nm. A linear form of the Benesi−Hildebrand equation yields a binding constant of 4.40 × 10 3 M −1 at 25 °C, establishing the self-consistency of our results obtained from absorption and fluorescence titrations. The competitive displacement reactions of dyes like ethidium bromide, Hoechst, and DAPI (4′,6-diamidine-2′-phenylindole dihydrochloride) from dye−ct-DNA conjugates by 1•H 2 O were analyzed, and the corresponding K SV values are 1.05 × 10 4 , 1.25 × 10 4 , and 1.35 × 10 4 M −1 and the K app values are 2.16 × 10 3 , 8.34 × 10 3 , and 9.0 × 10 3 M −1 , from which it is difficult to infer the preference of groove binding over intercalation by these DNA trackers. However, the molecular docking experiments and viscosity measurement clearly indicate the preference for minor groove binding over intercalation, involving a change in Gibbs free energy of −8.56 kcal/mol. The 1•H 2 O complex was then evaluated for its anticancer potential in breast cancer MCF-7 cells, which severely abrogates the growth of the cells in both 2D and 3D mammospheres, indicating its promising application as an anticancer drug through a minor groove binding interaction with ct-DNA.