【作者】 梁剑鸣；

【导师】 刘建利；

【作者基本信息】 西北大学 ， 生物化学与分子生物学， 2011， 硕士

【摘要】 细菌耐药性问题日益突出并严重威胁人类健康。研究表明外排泵是细菌耐药的重要机制。外排泵位于耐药菌株内膜上,可将药物自细胞内排至周质及胞外,降低抗菌药物在细菌细胞内的有效浓度。有些化合物本身无明显抗菌活性但可抑制细菌外排作用,这类化合物称为外排泵抑制剂。外排泵抑制剂与抗菌药物联用能有效对抗耐药菌。因此对其研究与开发有望成为恢复药物敏感性,解决耐药性问题的重要途径。本文合成一系列外排泵抑制剂类似物并对其抗菌活性做了初步研究,另外还对具有抗菌活性的水杨酰苯胺衍生物的合成做了一些探索。第二章以槲皮素和异丁香酚为原料合成了黄酮木质素类化合物I,并通过质谱,核磁氢谱进行了表征,该化合物未见文献报道；合成了9个吡啶二羧酸酯类化合物,并通过溶剂和催化剂的选择对反应条件进行了优化；以芳香酮和4-硝基苯肼为原料合成2-芳基-5-硝基吲哚。第三章以水杨酸和对氨基酚为原料对水杨酰苯胺类化合物的合成做了一些探索。第四章以固体平板抑菌圈和液体最低抑菌浓度测定法对部分化合物的抗菌活性进行了研究。结果表明这些化合物与环丙沙星联用可降低环丙沙星的最低抑菌浓度,有效抑制金黄色葡萄球菌耐药菌株。另外化合物I与左氧氟沙星、小檗碱联用时也表现出良好的抗耐药活性。更多还原

【Abstract】 Bacterial resistance is an increasingly serious problem which threatening the human and animals. Research shows that efflux pump of bacterial is an important mechanism of the resistance. Efflux pump which exists on the intracellular membrane of drug-resistant strains can decrease the effective concentration inside of bacterial by pump out drug from cells. Inhibitor of efflux pump has no effective antibacterial activity itself. But it could reverse the drug resistance by inhibiting the efflux pump. So the research and development of efflux pump inhibitor may become an important way to solve the problem of bacterial resistance. In this dissertation, the analogues of known efflux pump inhibitors were designed and synthesized and their antimicrobial activity were evaluated. The salicylanilide analogues which possess antibacterial activity were also synthesized.In the Chapter Two, a new flavone was synthesized from quercetin and isoeugenol and characterized by MS and 1HNMR. Nine 2,6-dimethyl-4-arylpyridine-3,5-dicarboxylic acid diethyl esters were synthesized and characterized. The reaction conditions were optimizing by choosing suitable solvent and catalyst. The synthesis of 2-aryl-5-nitro-lH-indoles was explored use aromatic ketones and 4-Nitrophenylhydrazine as starting material. The synthesis of salicylanilide analogues was explored in the Chapter Three.In the Chapter Four, the antimicrobial activity of some synthetic compounds combined with antibacterial drugs was evaluated. Inhibition zone and minimal inhibitory concentration were used as evaluation criterion. The mixture of Ciprofloxacin and any one of these compounds can lower the minimal inhibitory concentration of Ciprofloxacin in drug resistant strains, therefore they can inhibit the drug resistant strains of Staphylococcus aureus effectively.更多还原