Studies On Synthesis And Bacteriostasis Of Derivatives Of Quinoxaline-1,4-Dioxide And Its Interaction With Serum Albumin

According to little adverse reaction and more bioactivity of the derivatives of quinoxaline-1,4-dioxide, the thesis has synthesized three new derivatives of quinoxaline-1,4-dioxide, and had been characterized by means of elemental analyses, MS, IR and 1H NMR. The antibacterial activity experiment of CⅠ～CⅢwas carried by disk diffusion method and minimum inhibitory concentration(MIC) method to study the antibacterial activity. And the interaction between CⅠ～CⅢand bovine serum albumin (BSA) was studied by means of spectra on the basis of the binding site of biology big molecule and medicine small molecule interaction.Use o-nitroaniline as raw material, and aquire the target derivatives of quinoxaline-1,4-dioxide (CⅠ～CⅢ) though NaClO oxidizing reaction, Beirut reaction, SeO2 oxidizing reaction and condensation reaction. We improved SeO2 oxidizing reaction on the basis of predecessor , which use 1,4-dioxane as resolution, add required amount of SeO2 at one time, took 5 hours in the 100℃oil bath. And the intermediate product (2-ethylformate-3-formaldehyde quinoxaline-1,4-dioxide) was not necessary to been purified, was directly made use of condensation reaction, total yield was 76%.The antibacterial results showed that CⅠ～CⅢhad strong inhibitory activity against six trialed bacteria (i.e. Escherichia coli,Bacillus subtilis,Staphlococcus aureus,Bacillus megaterium,Sporosarcina urea,Bacillus thuringiensis), but no inhibitory activity against fungi(Penicillium,Phizopussp,Aspergillus niger) was observed. MIC of CⅠto Escherichia coli is 20μg·mL-1 and to Bacillus megaterium is l5μg·mL-1; MIC of CⅡto Escherichia coli is 10μg·mL-1 and to Staphlococcus aureus is l5μg·mL-1; MIC of CⅢto Escherichia coli is 15μg·mL-1 and to Bacillus thuringiensis is 20μg·mL-1.The interaction between Quinoxaline-1,4-dioxide(CⅠ～CⅢ) and bovine serum albumin (BSA) was studied by fluorescence spectra and ultraviolet spectra. The binding constant K and the binding sites n were found by fluorescence quenching method. The binding distance r and energy-transfer efficiency E between CⅠ～CⅢand BSA were also obtained according to the Forster-type dipole-dipole non-radiative energy-transfer mechanism. The effect of CⅠ～CⅢon the conformation of BSA was also analyzed by using synchronous fluorescence spectroscopy. In additional, the impact of CⅠ～CⅢon conformation of BSA was examined by synchronized spectrum, the hydrophobic interaction between CⅠ～CⅢand BSA is strong, and CⅠ～CⅢcan effect the conformation of BSA in some degree. According to it, we will obtain that CⅠ～CⅢmay reach to recipient and take an action by storing and carrying of blood plasm.