Structure and biological properties of the copper(II) complex with the quinolone antibacterial drug N-propyl-norfloxacin and 2,2'-bipyridine

The neutral mononuclear copper complex with the quinolone antibacterial drug N-propyl-protected norfloxacin, Hpr-norfloxacin, in the presence of the nitrogen donor heterocyclic ligand 2,2'-bipyridine has been prepared and characterized. The crystal structure of (chloro)(2,2'-bipyridine)(pr-norfloxacinato)copper(II), 1, has been determined and refined with X-ray crystallography. X-band electron paramagnetic resonance (=EPR) spectroscopy at liquid helium temperatures from powdered samples indicates the presence of dimeric units in consistency with the crystal structure. In aqueous solutions of 1 the EPR behavior indicates mixture of dimeric and monomeric species. The antimicrobial activity of the complex has been tested on three different microorganisms and the best inhibition (MIC = 0.25 mu g mL(-1)) has been exhibited against Escherichia coli. The study of the interaction of the complex with calf-thymus DNA has been performed with diverse spectroscopic techniques and has shown that complex I is bound to calf-thymus DNA by the intercalative mode. Potential anticancer cytostatic and cytotoxic effects of complex I on human promyelocytic leukemia HL-60 and human chronic myelogenous leukemia K562 cell lines have been investigated. Complex I shows an increased antiproliferative and necrotic effect on both HL-60 and K562 human leukemia cells in comparison to the free pr-norfloxacin. (c) 2006 Elsevier Inc. All rights reserved.