Biological activities of Cu(II) and Hg(II) complexes of a heptadentate Schiff base ligand

Abstract

Two metal complexes were synthesized as [Hg(L)](ClO4)(2) and [Cu(L)](ClO4), by the template reaction between 2,6-bis(2-aminothiophenoxymethyl)pyridine and 2,2'-bipyridine-6,6'-dicarboxaldehyde in the presence of Hg(II) and Cu(II) perchlorate salts. The structures of the compounds were elucidated by IR, H-1-NMR, MASS, and Elemental Analyses values. Cytotoxicity of the compounds were investigated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay in normal and cancerous rat fibroblasts. Both compounds showed cytotoxicity on 2 cell lines as a dose-dependent manner. Compound [Hg(L)](ClO4)(2) was more cytotoxic than [Cu(L)](ClO4)(2). Apoptotic activity of compounds was evaluated by acridine orange staining and DNA fragmentation assay. Both cell lines exposed to the compounds exhibited condensed chromatin and appearance of apoptotic bodies. The percentages of all these abnormalities were found to be very high level in ras-transformed 5RP7 fibroblasts. The effect of [Hg(L)](ClO4)(2) was again more stronger than the compound [Cu(L)](ClO4)(2). Although the compound [Cu(L)](ClO4)(2) induced the formation of DNA fragmentation in both cell lines, [Hg(L)](ClO4)(2) induced the DNA fragmentation only in cancerous 5RP7 cells, indicating specific activity. In conclusion, we suggest that both complexes, especially the one with Hg(II) according to its significant differences of apoptotic morphology and DNA fragmentation, exhibit promising potentials as anticancer compounds.