Anticancer Applications of New Nickel(II) Complexes with Detoxicant Ligands

Abstract

Herein a new series of nickel(II) dithiocarbamates has been synthesized by reacting nickel(II) chloride with sodium salts of dithiocarbamates in methanol solvent. The ligands used were sodium 4-benzylpiperidine-1-carbodithioate (L-1), sodium di-secbutylcarbamodithioiate (L-2), sodium 4-(pyridin-2-yl)piperazine-1-carbodithioate (L- 3), sodium 4-(2-hydroxyethyl)piperazine-1-carbodithioate (L-4), sodium 4-(3- methoxyphenyl)piperazine-1-carbodithioate (L-5), sodium 4-(pyrimidin-2- yl)piperazine-1-carbodithioate (L-6). The coordination mode of ligands towards Ni(II), structural confirmation and geometry assignment of the complexes was made using different analytical techniques such as elemental analysis, FT-IR, multinuclear ( 1H and 13C ) NMR and single crystal X-ray diffraction technique. Single crystal X-ray analysis has confirmed the anisobidentate nature of dithiocarbamate ligand resulting in ideal square planer geometry for C5. UV–Vis and viscometric titration techniques have been employed to probe the details of DNA binding. The hypochromic effect for all the complexes was observed, indicating intercalative mode of interaction and intrinsic binding constants (Kb) have been estimated under a similar set of experimental conditions. Antiproliferative activity of all synthesized compounds was assessed against MCF-7 (human breast cancer cell line). Results showed that all the complexes were significantly active against MCF-7 (human breast cancer cell line) but the C4 exhibit pronounced activity. A brief account of computational technique is described using B3LYP/LANL2DZ level of Density Functional Theory in Gaussian 09 that can be used as a dynamic tool with a specific end goal to achieve profound information regarding the parameters requisite for the stabilization of coordination compound-DNA adduct.