Association of late transition metal complexes with ethyl 2-(2-(4-chlorophenylcarbamothioyl)hydrazono)propanoate: Design, synthesis and in vitro anticancer studies

•A novel chelating ligand (LH) and its metal complexes were synthesized and characterized.•Crystal structure of LH was determined by single crystal X-ray diffraction analysis.•In vitro antiproliferative activity of panel of complexes synthesized was evaluated.•Cu-L showed IC50 values 15.16 and 8.65 μM for K-562 and COLO-205, respectively.•Cu-L antiproliferative effect was exerted through the induction of apoptotic cell death.

A newly synthesized chelating agent ethyl 2-(2-(4-chlorophenylcarbamothioyl)hydrazono)propanoate with SNO donor sites is employed for the synthesis of Co(II), Ni(II), Cu(II) and Zn(II) complexes. Structure of ligand is determined by single crystal X-ray diffraction analysis. Octahedral geometry is assigned to all the complexes based on the physical and spectral data. The copper complex has shown redox responses in the applied voltage range, whereas the ligand and other complexes are electrochemically inactive. The new complexes synthesized have been evaluated for in vitro antiproliferative activity against human cancer cells of different origin such as COLO-205 and K-562. Among the compounds tested for their antiproliferative activity, IC50 value of copper complex is 15.16 and 8.65 μM for K-562 and COLO-205, respectively. Time dependent significant fall in mitochondrial membrane potential (ΔΨm) without generating reactive oxygen species (ROS) is observed in COLO-205 cells treated with copper complex, whereas its antiproliferative effect mediated by the induction of apoptotic cell death is evidenced by the sub-G0/G1 cells accumulation, oligonucleosomal DNA fragmentation, caspase-3 activation and the nuclear condensation. Further results confirmed subsequent apoptosis induction through activation of intrinsic apoptotic pathway.

Graphical abstractA novel chelating agent LH and its later Ist row transition metal complexes were synthesized and characterized. Crystal structure of ligand was determined by single crystal X-ray diffraction analysis. The new complexes synthesized have been evaluated for in vitro antiproliferative activity against COLO-205 and K-562 human cancer cells. Copper complex showed exceptional activity with IC50 values 15.16 and 8.65 μM for K-562 and COLO-205, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide