Synthesis and use of dioxime ligands for treatment of leukemia and colon cancer cells

Two new vicinal dioxime ligands containing thiosemicarbazone units ((LH2)-H-1 and (LH2)-H-2) were synthesized and characterized using H-1 NMR, C-13 NMR, heteronuclear multiple quantum correlation, mass, infrared and UV-visible spectroscopies, elemental analysis and magnetic susceptibility measurements. In addition, homotrinuclear nickel(II), copper(II) and cobalt(II) complexes with a metal-to-ligand ratio of 3:2 for (LH2)-H-1 and (LH2)-H-2 were prepared. Synthesis of nickel(II) complex containing a BF2+ bridge was carried out using a precursor hydrogen-bridged nickel(II) complex via the template effect. All metal-ligand complexes were tested against two human cancer cell lines (HL-60 and HT-29) for their antiproliferative and apoptotic activities. The results showed that [Co((LH)-H-2)(2)(H2O)(2)] and [Ni((LH)-H-2)(2)] exhibited the strongest antiproliferative activity with IpC50 values ranging between 5 and 10M, while [Co((LH)-H-2)(2)(H2O)(2)] and [Ni((LH)-H-2)(2)] both induced necrosis of HT-29 cells and 60 and 65% apoptosis in HL-60 cells, respectively.