Investigating the antiproliferative activities of new CuII complexes with pyridine hydrazone derivatives of nalidixic acid.

To further explore the structural features and potential antibacterial and antitumor activities of polynuclear CuII coordination compounds with nalidixic acid (nx) derivatives, new complexes bearing nx hydrazones with N-pyridinyl moieties substituted at positions 2 and 3 (h2py and h3py) were synthesized. Complexes [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)]4BF4∙H2O (1), and [Cu3(C18H16N5O2)2(C18H17N5O2)2(H2O)3]4BF4∙3H2O (%) (2) were synthesized using h2py and h3py with Cu(BF4)2∙nH2O as precursor, whereas the [Cu(C18H17N5O2)Cl2]∙0.5H2O complex (3) was synthesized with h2py and CuCl2∙2H2O. Crystallographic studies of complex 1, showed that coordination of hydrazones to CuII occurs by tridentate modes of type κ3(O,N,N') as well as bidentate modes of type κ2(O',N″). Complexes 1, 2 and 3 had their antiproliferative activities evaluated in vitro against a panel of tumor cells by the determination of GI50 values. Complexes 1 and 2 were more active than complex 3, suggesting an effect of the complex charge on their activities. The interactions of such complexes towards bovine serum albumin (BSA) and DNA plasmid (pGEX-4 T1) were investigated using fluorescence spectroscopy and gel electrophoresis. All complexes were shown to interact with the DNA model as metallonucleases, but no interaction with BSA was observed. DNA molecular docking of complex 1 encompassing both its trinuclear (TN) form and a possible mononuclear (MN) derivative suggests that naphthyridyl ring performs π-stacking interactions with DNA. The TN species were also shown to be possible minor groove binders.