2′-Thiophenecarboxaldehyde derived thiosemicarbazone metal complexes of copper(II), palladium(II) and zinc(II) ions: Synthesis, spectroscopic characterization, anticancer activity and DNA binding studies

Abstract

Heterocyclic 5′-methyl-2-thiophenecarboxaldehyde-N(4)-un/substituted thiosemicarbazones (1–3) and their metal complexes with copper(II), palladium(II) and zinc(II) ions (4–11) were synthesized and characterized by using different spectroscopic techniques like FT-IR, 1H, 13C NMR, UV–Visible and electron paramagnetic spectroscopy, etc. The crystal structures of the synthesized thiophene thiosemicarbazone ligands 1, 2 and 3 were determined unambiguously by single-crystal X-ray diffraction analysis. The EPR spectra of the copper(II) complexes, 4, 6 and 9 have shown rhombic, normal axial and inverse axial symmetry respectively. Furthermore, the DNA binding study was performed on calf-thymus DNA by absorbance, fluorescence and viscosity measurement methods. Notably, the copper(II) and palladium(II) complexes have strong DNA binding interactions compared to the zinc(II) complexes. The DNA binding constants measured for these complexes were found to be in the range of 1.83 × 104–1.45 × 105 M−1. Further, the newly synthesized complexes were also tested for their in vitro anticancer activity against three types of human cancer cell lines (COLO-205, MCF-7 and HepG-2) and one normal cell line (HEK-293). Importantly, the zinc(II) complex (8) exhibited potent anticancer activity against HepG-2 with an IC50 value of 11.65 ± 1.753 µM compared to the standard drug cis-platin. The copper(II) complex, 9 against COLO- 205 with an IC50 value of 23.08 ± 1.354 µM, complex 4 against MCF-7 and HepG-2 with IC50 values of 39.35 ± 1.825 µM and 35.26 ± 0.354 µM, respectively, and complex 6 against HepG-2 with an IC50 value of 38.30 ± 1.385 µM have displayed moderate activity compared to the reference drug cis-platin.