Synthesis, Characterization, Antibacterial And Antitumor Activities Of Metal Complexes With Quinolones

Quinolones is a kind of synthetic antibacterial agents with excellent activity, wide spectrum and low toxicity, which has been used widely in clinical practice for the efficient treatment of a variety of infections. Nowadays, quinolones has been one of the most important bacteriophage. However, there are some difficulties in the study of the exact mechanism of the antibacterial action, the bacteria resistance and further development of quinolone and its complexes. Based on the metal ions special position and important biological functions in the action of qunilones, the synthesis of complexes or compounds of drug ligand has. important meaning on theory and instructing practice, from the point view of mechanism study and inorganic medicine research. The study of complexes is mostly concentrated in structural characterization, at present, while less in property; the research objects are mainly nalidixic acid, norfloxacin and ciprofloxacin, while little work has been done to study metal complexes of ofloxacin and pazufloxacin. There are only few reports on the antitumor activity of quinolone complexes. Therefore, we do some works for these problems as follows:1. Coordination compounds formed between transition series metal ions and rare ions with ofloxacin (oflo), ciprofloxacin (tip) and pazufloxacin (pazu) as ligands have been synthesized. The isolated solid complexes were characterized by elemental analysis, Fourier transform infrared spectroscopy, UV-Vis spectrum, fluorescence spectroscopy and ¹H NMR spectrum.2. The thermal behavior of complexes in N₂ atmosphere was investigated by TG -DTG-DSC techniques. The non-isothermal kinetic data such as energy of activation (E), frequency factor (A) were analyzed by means of the Achar method and the Coants-Redfem method. The thermodynamic data such as the enthalpy of activationâ–³H, the entropy of activationâ–³S and the free energe of activationâ–³G were also calculated. General mechanisms describing the decomposition of the solid complexes were suggested. 3. A new ofloxacin-metal complex Zn(oflo)₂ (H₂O)·2H₂O was prepared by a hydrothermal reaction under basic conditions, which was characterized by single crystal X-ray determination, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal analysis. Crystal structure of Zn(oflo)₂ (H₂O)·2H₂O shows that Zn(â…¡) cation which displays a slightly distorted tetrahedral geometry is coordinated to tow oflo ligands related by the inversion center. Each oflo acts as bidentate ligand bonded to the cation through the ring carbonyl oxygen and the oxygen atom of a carboxylic group.4. Reactions of the antimicrobial fluoroquinolone oflo with Cu(NO₃)₂·3H₂O in the presence of N-N ligand o-phenanthroline(phen) under basic conditions produced a new metal-oflo complexes, namely, [Cu(oflo)(phen)(H₂O)](NO₃). 10H₂O, which was also characterized by single crystal X-ray determination, Fourier transform infrared spectroscopy, fluorescence spectroscopy and thermal analysis. Oflo acts as bidentate ligand bonded to the Cu(â…¡) ion through the oxygen atoms of the 3-carboxylate and 4-keto group. Phen is coordinated to Cu²⁺ through two N toms.5. In vitro inhibitory effects of the compounds we synthesized and the drug ligands on two tumuor cell lines, including HL-60 and BEL-7402, have been measured by using MTT (Methyl-Thiazol-Tetrozolium) assay and SRB (Sulphurhodamin B) assay. The results indicate that five complexes have inhibitory effect on HL-60, and five complexes on BELo7402. The complexes and three quinolone compounds were screened for their activities against the one gram-negative bacterium and two gram-positive bacteria. The results of the in vitro antimicrobial activity indicate that all complexes have the same minimal inhibitory concentration (MIC) and spectrum of the acticity as the corresponding ligand.