Inositol hexaphosphate (InsP6) is present in cereals, legumes, nuts and seed oils and is biologically active against some tumor and cancer cells. Herein, this study aimed at evaluating the cellular toxicity, antiproliferative activity and effects on cell cycle progression of free InsP6 and InsP6-Ni(II) of leukemic T (Jurkat) and normal human cells. Treatments with InsP6 at concentrations between 1.0 and 4.0mM significantly decreased the viability of Jurkat cells, but showed no cytotoxic effect on normal human lymphocytes. Treatment with InsP6-Ni(II) complex at concentrations between 0.05 and 0.30 mM showed an anti-proliferative dose and a time-dependent effect, with significantly reduced cell viability of Jurkat cells but showed no cytotoxic effect on normal human lymphocytes as compared to the control. Ni(II) free ion was toxic to normal cells while InsP6-Ni(II) had no cytotoxic effect. The InsP6-Ni(II) complex potentiated (up to 10×) the antiproliferative effect of free InsP6 on Jurkat cells. The cytometric flow assay showed that InsP6 led to an accumulation of cells in the G0/G1 phase of the cell cycle, accompanied by a decrease in the number of cells in S and G2/M phases, whereas InsP6-Ni(II) has led to an accumulation of cells in the S and G2/M phases. Our findings showed that InsP6-Ni(II) potentiates cytotoxic effects of InsP6 on Jurkat cells and may be a potential adjuvant in the treatment of cancer.

Cimetidine is an important hydrogen histamine receptor which has the ability to chelate metal ions in blood plasma and in different tissues. This study aimed to determine the stability constants for the cimetidine ligand with Mn II and Ni II metallic ions, synthesizing complexes and characterizing them by infrared spectroscopy, IR, and hydrogen nuclear magnetic resonance, 1 H NMR. Cimetidine protonation constant regarding to the imidazole group was logK 7.05 and the stability constants for Mn II and Ni II complexes, ML 2 species were logK 3.75 and 2.97, respectively, in 0.100 mol L -1 KCI. The interpretation of IR and H 1 NMR spectra for complexes Mn II -cim 2 and Ni II -cim 2 indicated that their formation occurs through the sulfur atoms in the thiol group, nitrogen atoms of imidazole ring, and nitrogen atoms of secondary amine. The nitrile group seems to be involved in the complexation of the Ni II -cim 2 complex.