Iron(III) and Nickel(II) Complexes as Potential Anticancer Agents: Synthesis, Physicochemical and Structural Properties, Cytotoxic Activity and DNA Interactions

Abstract

Template reactions of 2-hydroxy-R-benzaldehyde-S-methylisothiosemicarbazones (R = 3-methoxy or 4-hydroxy) with the corresponding aldehydes in the presence of FeCl<inf>3</inf> and NiCl<inf>2</inf> yielded N1,N4-disalicylidene chelate complexes. The compounds were characterized by means of elemental and spectroscopic methods. The structure of complex 1 was determined by X-ray single crystal diffraction. Crystal data (Mo Kα; 296 K) are as follows: monoclinic space group P2<inf>1</inf>/c, a = 12.9857(8) Å, b = 7.8019(4) Å, c = 19.1976(12) Å, β = 101.655(5)°, Z = 4. Cytotoxic effects of the compounds were evaluated by the MTT assay in K562 leukemia, ECV304 endothelial and normal mononuclear cells, and DNA fragmentation analysis using the diphenylamine reaction was performed. The DNA binding capacity of thiosemicarbazones at IC<inf>50</inf> and different concentrations was investigated. The DNA fragmentation percentage of compound treated cells was higher than that of non-treated control cells but was higher for compound 3 (84%) compared to the others. The interaction of compounds 1-4 and DNA was investigated voltammetrically by using nucleic acid modified electrodes after the double stranded fish sperm DNA (fsDNA), or poly(dA)·poly(dT), was immobilized onto the surface of pencil graphite electrodes (PGEs). Accordingly, the oxidation signals of DNA bases, guanine and adenine, were measured by using differential pulse voltammetry (DPV). The changes in the signals of guanine and adenine were evaluated before and after the interaction process. The results indicated that compound 3 was cytotoxic at very low concentrations in K562 leukemia cells unlike other cells and that could damage the DNA double stranded form, specifically the adenine base. Therefore, it may have a selective antileukemic effect and drug potential. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015.