Interaction Between Quinolones And Biomacromolecules As Well As Characterization And Biological Activities Of Pefloxacin Complexes

Quinolone 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, quinolone is 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. Protein and DNA are important bio-macromolecules in the life; they have respective biological functions and have been playing many vital roles for all kinds of biological phenomena. Exploring the interaction mechanisms on these bio-macromolecules with small molecules or ions, especially for those targeting-drug molecules, at the molecular level, is of current interest in many research areas. This paper studied the interaction mechanisms among quinolone drug, metal ions and bio-macromolecules.Based on the metal ions special position and important biological function 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. Therefore, we do some works for these problems as follows:1. The binding characteristics and mechanism of quinolone antibiotic Garenoxacin to DNA have been investigated by using the methods of fluorescence spectroscopy, absorbance spectroscopy and viscosity. The spectroscopy analysis shows that Garenoxacin can directly affect on DNA.Different metal ions can quench the endogenous fluorescence of the quinolone drug, and the fluorescence intensity of quinolone drugs quenched by calf thymus DNA was aggravated in the presence of metal ions. Based on the change of fluorescence intensity and fluorescence quench formulas, the quenching constants and resultant constants between DNA and quinolone drugs have been worked out, and the results show that the fluorescence quenching effect of DNA on quinolone is because of a static energy transfer mechanism.The experimental results of viscosity show that the binding mode of quinolone with DNA is part of intercalation binding.2. The binding characteristics and mechanism of quinolone antibiotics to BSA have been investigated by using fluorescence spectroscopy and absorbance spectra. Garenoxacin can quench the endogenous fluorescence of BSA regularly and the quenching was not initiated by dynamic collision but from compound formation, it was a static quenching process. The interaction between Garenoxacin and BSA in the presence of metal ions was also studied.3. The binding characteristics and mechanism of quinolone antibiotic Balofloxacin to DNA have been investigated by using the methods of fluorescence spectroscopy, absorbance spectroscopy. The spectroscopy analysis shows that Balofloxacin can directly affect on DNA. Based on the change of fluorescence intensity and fluorescence quench formulas, the quenching constants and resultant constants between DNA and Balofloxacin have been worked out, and the results show that the fluorescence quenching effect of DNA on quinolone is because of a static energy transfer mechanism, and the number of binding sites between DNA and quinolone were deduced to be 1. The experimental results of absorbance spectroscopy show that the binding mode of quinolone with DNA is electrostatic binding.4. A new Pefloxacin-metal ionic compound,2(C17H21FN3O3)·CdCl4·H2O, was prepared,which has been characterized by single crystal X-ray determination, Fourier transform infrared spectroscopy. In vitro inhibitory activities of the compound and the drug liagand on 7721 tumor cell line have been measured by using MTT (Methyl-Thiazol-Tetrozolium) assay method,but the result is not satisfactory.5. A new pefloxacin-copper complex, [Cu(pef)(phen)(H2O)](NO3)·2H2O, was prepared, which has been characterized by single crystal X-ray determination, Fourier transform infrared spectroscopy. Crystal structure of this complex shows that Cu(Ⅱ) cation which displays a slightly distorted tetrahedral geometry is coordinated to tow pef ligands related by the inversion center. Each pef acts as bidentate ligand bonded to the cation through the ring carbonyl oxygen and the oxygen atom of a carboxylic group. In vitro inhibitory activities of the compound and the drug liagand on 7721 tumor cell line have been measured by using MTT (Methyl-Thiazol-Tetrozolium) assay method. The result shows that the activity is not satisfactory.