Synthesis, Antitumor Activity Of Quinolone Compounds Containing Palladium And Study On The Interaction Of Phenanthroline Metal Complex With DNA

This paper study mainly on synthesis, crystal structure, antitumor of quinolone compounds containing palladium, and synthesis, crystal structure of norfloxacin picrate supremolecular compound. The interaction of quinolones with DNA and the factors which effect interaction of quinolones with DNA also were studied. Meanwhile the interaction between phenthroline metal complex and DNA were studied by spectroscopy. By molecular surface electrostatic potential method, the quantitative structure-activity relationship(QSAR) of quinolone was studied. The paper is composed of following parts:1. Synthesis and characteristic of quinolone compound containing palladium and study on interaction between quinolone compound and DNA. The quinolone (norfloxacin, ciprofloxacin, ofloxacin and ernofloxacin) compounds containing palladium were synthesized for the first time. Among them, the norfloxacin compound containing palladium is orange crystal, the other are yellow powder. Analyzed by method of X-ray diffraction, the crystal structure of norfloxacin compound has obtained: (NFLXH)₂[PdCl₄]·2H₂O. By the method of elemental analysis, IR, UV and TG, the structure of another three quinolone compounds were characterized. According to the characteristic results and the crystal structure of norfloxacin compound, the structure of the ciprofloxacin, ofloxacin, enrofloxacin compounds were deduced: (CPLXH)₂[PdCl₄]·2H₂O, (OFLXH)₂[PdCl₄]·2H₂O, (ERLXH)₂[PdCl₄]·2H₂O. By method of ultraviolet absorption spectroscopy and fluorescence spectroscopy, the interaction between quinolone compounds and DNA were studied. The results show there are interaction between quinolone compounds and DNA. The type of interaction might be intercalative binding mode.2. Study on the interaction between quinolones and DNA by method of ultraviolet absorption spectroscopy and fluorescence spectroscopy. The interaction between quinolone and DNA were studied, and the binding constant of quinolone and DNA were obtained. Meanwhile the effects of La³⁺, Cu²⁺ on spectra of quinolone and DNA were studied. The studies indicated there are interaction between quinolone and DNA, The binding capability is: enrofloxacin＞ciprofloxacin＞ofloxacin＞norfloxacin. The study about metal ions effect on interaction between quinolone and DNA shows La³⁺ make system of quinolone-DNA produce hyperchromic effect, whereas Cu²⁺ make system of quinolone-DNA produce hypochromic effect.Synthesis,crystal structure of norfloxacin picrate supramolecular compound and study on the interaction between norfloxacin picrate and DNA. In mixed solvent of acetonitrile and ethanol, norfloxacin picrate supramolecular compound was synthesized. The crystal structure of the compound consists of norfloxacin cations and picric acid anions. It is built up by intermolecular and intramolecular hydrogen bonds. By method of ultraviolet absorption spectroscopy and fluorescence spectroscopy, the interaction between norfloxacin picrate and DNA were studied. Compared with the benzene or norfloxacin, the norfloxacin has stronger interaction with DNA, for it can form supramolecule by hydrogen bonds, which make norfloxacin intercalate more strongly.3. Study on the antitumor activity and antibacterial activity of the quinolone compounds containing palladium. Antitumor activity and antibacterial activity of the quinolone compounds containing palladium were tested. The results showed that the quinolone compounds containing palladium have antitumor activity and can inhibit HL-60 cell, A549 cell growth. The antitumor activity of (CPLXH)₂[PdCl₄]·2H₂O is better than that of (NFLXH)₂[PdCl₄]·2H₂O. The results also showed that the quinolone compounds containing palladium have antibacterial activity.4. Study on the quantitative structure-activity relationship(QSAR) of the quinolone. By method of quantum chemistry and multiple regression analysis model, the relationships between the structure descriptor of quinolone and inhibition of OR-gyrase activity, inhibition of TOPO-â…¡activity, difference of activity have been built. The formula of QSAR are ideal, for the correlation coefficient R＞0.9. By the formula of QSAR, the activity of quinolone can be calculated.5. The interaction between [Zn(phen)₂]²⁺ complex ion and DNA was investigated by absorption spectra,fluorescence spectra.Based on the measurement of A₂₆₀ in the different pH medias,the alkaline denaturation curves of DNA in the absence of and in the presence of [Zn(phen)₂]²⁺complex ion was obtained.The result showed that the alkaline denaturation for [Zn(phen)₂]²⁺complex ion occurred at a higher pH than for DNA alone. The absorption of EB-DNA system in the presence of [Zn(phen)₂]²⁺ showed that [Zn(phen)₂]²⁺ could partly sustain the place of EB. The result of fluorescence spectra suggested that the [Zn(phen)₂]²⁺complex ion could make the fluorescence intensity of EB-DNA system decreased sharply. All the experimental results indicated that the intercalative binding mode was the major modal for the interaction of [Zn(phen)₂]²⁺ complex ion with DNA.6. Study on the interaction between [Ce(NO₃)₃(phen)₂]and DNA by spectroscopy. The absorption spectra, fluorescence spectra and Raman spectra of [Ce(NO₃)₃(phen)₂] complex have been assigned and the crystal structure of the complex has been studied. Meanwhile the interactions between [Ce(NO₃)₃(phen)₂] and DNA have been researched by spectrum methods. When DNA added, it was found that the UV absorption spectra bands of [Ce(NO₃)₃(phen)₂] were weakened and the SERS bands of [Ce(NO₃)₃(phen)₂] were weakened evidently, while the fluorescence intensity of [Ce(NO₃)₃(phen)₂] were enhanced evidently. The complex competed against EB on the reaction with DNA. The study results of spectrum methods in this work indicated there are strong interaction between [Ce(NO₃)₃(phen)₂] and DNA, and the bind mode is intercalation mode. The bind of the complex and DNA is determined to be 1.7×10⁵...