Synthesis, crystal structure, theoretical calculation and cytotoxic effect of new Pt(ii), Pd(ii) and Cu(ii) complexes with pyridine-pyrazoles derivatives

The synthesis, structure and cytotoxic activity of Pt( II ), Pd( II ) and Cu( II ) complexes of the general formula MLCl 2  (M = Pt, Pd, Cu) 2–4 and (CuLCl 2 ) 2 5 where L is pyrazole-based chelate ligand 3-methyl-1-(2-pyridinyl)-1 H -chromene[4,3- c ]pyrazol-4-one 1 are described. The complexes were characterized by elemental analysis, infrared and 1H NMR spectroscopy, as well as electrospray mass spectrometry. Compounds 3 and 5 were also studied using X-ray diffraction. In addition, geometries, partial atomic charges, and lipophilicity, which determines their ability to penetrate through cells membranes, were obtained computationally. Complexes 2–4 exhibit square-planar geometries around the metal( II ) centers and adopt  cis  configuration. Complex 5 is a dimer with distorted tetragonal pyramidal configuration at both Cu( II ) centers, which are connected by two μ 2 -chloro bridges in axial positions. The cytotoxic effect of these complexes was examined on HL-60 and NALM-6 human leukemia cells and melanoma WM-115 cells. The Pt-complex  cis -2 exhibited moderate cytotoxic activity against leukemic cells, but relatively high activity toward melanoma cells with cytotoxicity of IC 50  = 16.6 μM at a level comparable to that of cisplatin (18.2 μM).