Synthesis, X-ray structure and in vitro cytotoxicity studies of Cu(i/ii) complexes of thiosemicarbazone: special emphasis on their interactions with DNA

Abstract

4-(p-X-phenyl)thiosemicarbazone of napthaldehyde {where X = Cl (HL¹) and X = Br (HL²)}, thiosemicarbazone of quinoline-2-carbaldehyde (HL³) and 4-(p-fluorophenyl)thiosemicarbazone of salicylaldehyde (H₂L⁴) and their copper(I) {[Cu(HL¹)(PPh₃)₂Br]·CH₃CN (1) and [Cu(HL²)(PPh₃)₂Cl]·DMSO (2)} and copper(II) {[(Cu₂L³₂Cl)₂(μ-Cl)₂]·2H₂O (3) and [Cu(L⁴)(Py)] (4)} complexes are reported herein. The synthesized ligands and their copper complexes were successfully characterized by elemental analysis, cyclic voltammetry, NMR, ESI-MS, IR and UV-Vis spectroscopy. Molecular structures of all the Cu(I) and Cu(II) complexes have been determined by X-ray crystallography. All the complexes (1-4) were tested for their ability to exhibit DNA-binding and -cleavage activity. The complexes effectively interact with CT-DNA possibly by groove binding mode, with binding constants ranging from 10⁴ to 10⁵ M⁻¹. Among the complexes, 3 shows the highest chemical (60%) as well as photo-induced (80%) DNA cleavage activity against pUC19 DNA. Finally, the in vitro antiproliferative activity of all the complexes was assayed against the HeLa cell line. Some of the complexes have proved to be as active as the clinical referred drugs, and the greater potency of 3 may be correlated with its aqueous solubility and the presence of the quinonoidal group in the thiosemicarbazone ligand coordinated to the metal.

DNA interaction and cytotoxic activity of copper complex based on tridentate hydrazone derived ligand and nitrogen donor heterocycle

“…Intrinsic binding constant for complex was found to be (4.02 ± 0.09) × 10 4 M − 1 comparable with the reported values [31,32].…”

A study of DNA/BSA interaction and catalytic potential of oxidovanadium(v) complexes with ONO donor ligands

“…Circular Dichroism (CD) spectroscopy was studied using a Chirascan CD spectropolarimeter (Applied Photophysics, UK) as described previously. 38 Briefly, the spectra of 150 μM of CT-DNA in the absence and presence of complexes (25 μM) were obtained in the wavelength range of 240-300 nm in 10 mM Tris-HCl buffer ( pH 8.0) containing 1% DMF using a quartz cell.…”

DNA binding behaviour of mixed ligand vanadium(V) complex based on novel tridentate hydrazone and benzhydroxamic acid ligand systems

“…[DNA]/( ε a − ε f ) versus [DNA] values were plotted and K b was obtained from the ratio of the slope to the intercept. K b values for the [VO(HL)(Benz)] complex and cisplatin were found to be (3.84 ± 0.08) × 10 4 M −1 and (4.27 ± 0.012) × 10 4 M −1 , respectively . The red shift in the absorption maxima of the complex was measured and Δ λ was found to be 0.7 nm, whereas in the case of cisplatin the shifts in the wavelengths were negligible.…”