截短侧耳素磺胺嘧啶衍生物的合成与抑菌效果研究
详细信息 查看官网全文
- 英文论文题名：Syntheses and Bacteriostatic Action of the Derivative of Sulfadiazine and Pleuromutilin
- 论文作者：余磊 ; 金学平 ; 熊海燕 ; 张婷
- 英文论文作者：Lei Yu ; Xueping Jin ; Haiyan Xiong ; Ting Zhang ; Department of Environment and Chemistry ; Wuhan Vocational College of Software and Engineering ; Wuhan Drug Solubilization and Delivery Technology Research Center
- 年：2016
- 作者机构：武汉软件工程职业学院环境与生化工程学院;武汉市药物増溶工程技术研究中心;
- 论文关键词：截短侧耳素磺胺嘧啶衍生物 ; 合成 ; 抑菌效果
- 英文论文关键词：derivatives of Sulfadiazine and pleuromutilin ; synthesis ; bacteriostatic action
- 会议召开时间：2016-10-14
- 会议录名称：第二届湖北省化学化工青年科学家论坛摘要集
- 语种：中文
- 分类号：TQ460.1
- 学会代码：HXGC
- 会议名称：第二届湖北省化学化工青年科学家论坛
- 会议地点：中国湖北武汉
- 主办单位：湖北省化学化工学会
- 学会名称：《化学与生物工程》编辑部
- 页数：2
- 文件大小：89k
- 原文格式：D
- 会议级别：地方
摘要
截短侧耳素(pleuromutilin)是Kavanagh和他的同事在上世纪50年代首次从高等真菌Pleurotus multilus(Fr.)Sacc.和Pleurotus Passecke-rianus Pilat中分离了一种具有抗菌活性的双萜类化合物。截短侧耳素及其衍生物是在核糖体水平上抑制细菌蛋白质的合成,研究表明,截短侧耳素及其衍生物作用于细菌核糖体50S亚基的23SRNA上,结合位点在肽基转移酶(PTC)的V结构域。其三元母核结合于A位点的活性口袋中,而侧链部分覆盖了tRNA与核糖体结合的P位点,通过抑制细菌蛋白质的合成而达到抑菌目的。构效关系研究表明截短侧耳素类衍生物C14位的侧链的羟基是可以改造的。通过对其改造,可以获得新的抗菌药物,增加截短侧耳素的抗菌效果、提高其水溶性和生物利用度。本研究用截短侧耳素与甲磺酰氯反应生成截短侧耳素甲磺酸酯,再与磺嘧啶胺反应,将磺胺嘧啶基团接枝在截短侧耳素侧链上,形成新化合物截短侧耳素磺胺嘧啶衍生物。利用质谱对目标产物进行表征。并研究了截短侧耳素磺胺嘧啶衍生物的溶解性和抑菌活性。结果表明,截短侧耳素磺胺嘧啶衍生物在水中成盐以后可溶,并对大肠杆菌和金黄色葡萄球菌有明显的抑制作用。
Pleuromutilin was first isolated in a crystalline form cultures of two species of basidiomycetes,Pleurotus mutilus and P. passeckerianus by Kavanagh and hiscolleagues in 1951. pleuromutilin derivatives interfered with bacterial protein synthesis via a specific interaction with the 23 S rRNA of the 50 S bacterial ribosome subunit. The domain V of 23 S r RNA at the peptidyl transferase center(PTC) is mutilins derivatives binding site, in which the tricyclic core of the pleuromutilin is positioned in a pocket close to the A-t RNA binding site, whereas the side chain extension points toward the P-t RNA binding site. Thus these compounds prevent the correct positioning of the t RNAs for peptide transfer, and inhibit the peptidyl trasferase. Structure activity relationship(SAR) studies showed that the hydroxyl of C-14 chain could be modified, so the molecular modifications of pleuromutilin could be the most promising approach to obtain optimum antibacterial, increasing its solubility and bioavailability. In this work, the pleuromutilin mesylate was prepared with pleuromutilin and methanesulfonyl, then the novel derivatives of Sulfadiazine and pleuromutilin was synthesized through coupling Sulfadiazine with pleuromutilin in the side chain, by the reaction of pleuromutilin mesylate and Sulfadiazine. The product was characterized by MS, also its solubility and antibacterial effect were studied. The results showed that the derivatives of Sulfadiazine and pleuromutilin was soluble in water by salifying, and showed bacteriostatic action against Escherichia coli and Staphylococcus aureus.
Pleuromutilin was first isolated in a crystalline form cultures of two species of basidiomycetes,Pleurotus mutilus and P. passeckerianus by Kavanagh and hiscolleagues in 1951. pleuromutilin derivatives interfered with bacterial protein synthesis via a specific interaction with the 23 S rRNA of the 50 S bacterial ribosome subunit. The domain V of 23 S r RNA at the peptidyl transferase center(PTC) is mutilins derivatives binding site, in which the tricyclic core of the pleuromutilin is positioned in a pocket close to the A-t RNA binding site, whereas the side chain extension points toward the P-t RNA binding site. Thus these compounds prevent the correct positioning of the t RNAs for peptide transfer, and inhibit the peptidyl trasferase. Structure activity relationship(SAR) studies showed that the hydroxyl of C-14 chain could be modified, so the molecular modifications of pleuromutilin could be the most promising approach to obtain optimum antibacterial, increasing its solubility and bioavailability. In this work, the pleuromutilin mesylate was prepared with pleuromutilin and methanesulfonyl, then the novel derivatives of Sulfadiazine and pleuromutilin was synthesized through coupling Sulfadiazine with pleuromutilin in the side chain, by the reaction of pleuromutilin mesylate and Sulfadiazine. The product was characterized by MS, also its solubility and antibacterial effect were studied. The results showed that the derivatives of Sulfadiazine and pleuromutilin was soluble in water by salifying, and showed bacteriostatic action against Escherichia coli and Staphylococcus aureus.
引文