COPPER(II) COMPLEXES WITH NOVEL N1-ACYLAMIDRAZONES AS LIGANDS:
SYNTHESIS STRUCTURAL CHARACTERIZATION AND ANTICANCER ACTIVITY
Liliana Agnieszka Mazur, B. Modzelewska-Banachiewicz, R. Bursa, J. Wietrzyk, K.
In recent years a considerable effort has been focused on the development of new metal-based
anticancer drugs with different modes of DNA interactions like hydrogen-bonding and π.π stacking
interactions that bind and cleave DNA under physiological conditions. [1, 2] Copper(II) complexes
seem to be the best candidates as they are less toxic than e.g. platinum derivatives, possess
biologically accessible redox potential and demonstrate high nucleobase affinity. Due to these
properties they can bind and cleave the DNA molecules under both oxidative and hydrolytic conditions.
The results of our research on novel N1-acylamidrazone derivatives and their Cu(II) complexes indicated that the latter
are of interest as potential antitumor drugs. The antiproliferative effect of the parent ligands and their Cu(II) complexes
was tested in vitro in the cultures of different [HT-29/CX-1, HL-60 and MCF-7] tumor cell lines. The tested metal
complexes significantly inhibited the growth of colon carcinoma cell lines (HT-29, CX-1). What is more, they exhibited
about 50-fold lower cell toxicity as compared to cisplatin, which makes them particularly interesting as drugs. Similarly,
very low toxicity was observed for the parent amidrazone ligands but their efficiency in tumor cell growth inhibition was
much lower. Thus, the pharmacological tests revealed that the coordination effect improves the biological activity of all
analyzed amidrazone ligands. However, the potential of the Cu(II) complexes studied so far depends on the type of
ligand as well as overall structure and composition of the complex.