Design, synthesis and X-ray structural studies of novel [acetonitrile-benzyl-3-N-(2, 4 dihydroxyphenylmethylene) hydrazinecarbodithioato-κ3-N′, S, O] nickel(ll) complex that potently inhibit cell proliferation through regulation of apoptosis related genes

Nickel is a fundamental element for healthy life for human and higher animals. For biological importance, its complexation with bioactive ligand is worth to be studied with the aim to understand its function. Using mouse peritoneal cancer model, MTT colorimetric assay and anticancer activity analysis, we examined the role of nickel(ll) complex in growth inhibition of cancer cells. A novel nickel(ll) complex was synthesized and characterized using physico-chemical and spectroscopic techniques. The study indicated that both the ligand and complex were capable of inhibiting Ehrlich Ascites Carcinoma (EAC) cells growth by 28.21% and 44.52%, respectively, when administered 0.3 mg/kg/day body weight intraperitoneally for five consecutive days in Swiss Webstar mice. Determination the LD50 of the complex (55 mg/kg) allowed adjusting the dose as 2.75 mg/kg and upon administration, inhibition increased to 69.36%. The ligand and complex have shown an inhibitory effect in the range of 4.86%-67.3% and 6.1%- 89.37%, respectively, against EAC cells (concentration range of 31.25-500 mu g/ml) in RPMI-1640 medium as determined by MTT colorimetric assay. Apoptotic cell morphological alteration was determined through optical and fluorescence microscopy. Up regulation of P-53, Bax, Cas-8, Cas-3 and Fas and down regulation of NF-kB and Bcl-2 gene expression were observed in the cells treated with the nickel(ll) complex for five consecutive days. In conclusion, the newly synthesized nickel(ll) complex has shown anti-proliferative activity and can further be optimized to be used as a lead molecule for anticancer drug.