4. Conclusions
HPyCT4BrPh and its copper(II) complex [Cu(PyCT4BrPh)Cl] (1), already known to be cytotoxic agents against HL60 leukemia cells, MDA-MB 231 and HCT-116 tumor cells, are shown to have cytotoxic effect also against THP-1 and MCF-7 cells. Coordination of the thiosemicarbazone to copper(II) improves the effect, making complex (1) more efficient than the parental compound (Table 1). In fact the ligand HPyCT4BrPh shows some cytotoxic activity, but upon coordination to copper(II) to form complex (1) the cytotoxic effect increases 6-fold against THP-1 leukemia cells and 8-fold against MCF- 7 solid tumor cells (Table 1). This effect is due to complex (1) since addition of CuCl2 does not induce any toxicity. Thiosemicarbazones have been suggested to exert their antineoplastic activity through several mechanisms such as Fe chelation, in this way being responsible for the iron impoverishment of the biological systems. They may also act through the redox cycling properties of the resulting FeII-thiosemicarbazones complex, inhibiting essential enzymes such as ribonucleotide reductase [42]. Other mechanisms are also described, such as inhibition of topoisomerase IIa, for which the binding of thiosemicarbazone to the ATP hydrolysis domain was shown to be responsible for enzyme inhibition [18].
