银杏酸类似物的合成及其灭螺活性的研究
发布时间：2018-07-13 21:29
【摘要】： 血吸虫病是一种严重危害人类健康和社会经济发展的重大传染性疾病。我国流行的是日本血吸虫病,近几年来疫情呈明显上升趋势。水陆两栖湖北钉螺(钉螺)是日本血吸虫的唯一中间宿主,控制钉螺是血吸虫病防治的关键技术之一。国家需求高效、低毒、价廉的新型灭螺药物替代化学合成的氯硝柳胺。很多植物都有一定的杀灭钉螺的作用,银杏外果皮的主要成分之一银杏酸显示了较强的灭螺活性。 银杏酸是银杏外果皮提取物的主要成分,也存在于银杏的果实和叶子中,是一类烷基或烯基酚酸化合物。已有研究表明其有较强的杀灭钉螺的作用,具有开发成高效、低毒、价廉的新型灭螺药物的潜力。我们拟合成一系列烷基酚酸,通过包括1)改变烷烃长链在酚酸母核上的位置;2)改变烷烃长链碳原子的数目等方法探讨不同结构的烷基酚酸与其灭螺活性的构效关系。同时,合成一系列具有氯硝柳胺类似结构的化合物,研究其构效关系,寻求一种新的对化合物的改造途径以改进化合物的灭螺活性。 最终我们合成了6个烷基酚酸和4个水杨酸酰胺,其中七个为新化合物,并对它们进行了灭螺活性和抑制钉螺上爬活性测试。结果显示,所合成的烷基酚酸均具有较好的灭螺活性。而且,通过不同化合物灭螺活性比较发现,酚羟基和羧基是其灭螺活性的必需基团,而烷烃长链碳原子的数目也在一定程度上影响其灭螺活性,在以上合成的烷基酚酸中,较短的碳链显示出了较强的灭螺活性和抑制钉螺上爬活性,为我们改造银杏酸结构、提高银杏酸灭螺活性提供了新的思路。
[Abstract]:Schistosomiasis is a major infectious disease that seriously endangers human health and social and economic development. Schistosomiasis japonicum is prevalent in China. Amphibious Oncomelania hupensis (Oncomelania hupensis) is the only intermediate host of Schistosoma japonicum. The country needs new snail-killing drugs that are efficient, low-toxic and inexpensive to replace chemically synthesized niclosamide. Many plants have a certain killing effect on Oncomelania hupensis, and ginkgolic acid, one of the main components of the exocarp of Ginkgo biloba, has strong snail killing activity. Ginkgolic acid is the main component of exocarp extract of Ginkgo biloba and also exists in the fruit and leaf of Ginkgo biloba. It is a kind of alkyl or alkyl phenolic acid compound. Studies have shown that it has a strong role in killing Oncomelania hupensis and has the potential to develop new snail killing drugs with high efficiency, low toxicity and low cost. A series of alkylphenolic acids were synthesized. The structure-activity relationship between alkyl phenolic acids with different structures and their spirocidal activity was studied by changing the position of long chain alkanes on the parent nucleus of phenolic acids and changing the number of carbon atoms in long chain of alkanes. At the same time, a series of compounds with similar structure of niclosamide were synthesized and their structure-activity relationships were studied. Finally, we synthesized 6 alkylphenolic acids and 4 salicylic acid amides, seven of which were new compounds, and tested them for snail killing activity and inhibiting snail climbing activity. The results showed that all alkyl phenolic acids had good snail killing activity. In addition, it was found that phenolic hydroxyl and carboxyl groups were the necessary groups for snail killing activity, and the number of long chain carbon atoms of alkanes also affected the snail killing activity to some extent. The short carbon chain showed stronger snail killing activity and inhibited snail climbing activity, which provided a new idea for us to modify the structure of ginkgo acid and improve the activity of ginkgo acid.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R284;R184
本文编号：2120795
[Abstract]:Schistosomiasis is a major infectious disease that seriously endangers human health and social and economic development. Schistosomiasis japonicum is prevalent in China. Amphibious Oncomelania hupensis (Oncomelania hupensis) is the only intermediate host of Schistosoma japonicum. The country needs new snail-killing drugs that are efficient, low-toxic and inexpensive to replace chemically synthesized niclosamide. Many plants have a certain killing effect on Oncomelania hupensis, and ginkgolic acid, one of the main components of the exocarp of Ginkgo biloba, has strong snail killing activity. Ginkgolic acid is the main component of exocarp extract of Ginkgo biloba and also exists in the fruit and leaf of Ginkgo biloba. It is a kind of alkyl or alkyl phenolic acid compound. Studies have shown that it has a strong role in killing Oncomelania hupensis and has the potential to develop new snail killing drugs with high efficiency, low toxicity and low cost. A series of alkylphenolic acids were synthesized. The structure-activity relationship between alkyl phenolic acids with different structures and their spirocidal activity was studied by changing the position of long chain alkanes on the parent nucleus of phenolic acids and changing the number of carbon atoms in long chain of alkanes. At the same time, a series of compounds with similar structure of niclosamide were synthesized and their structure-activity relationships were studied. Finally, we synthesized 6 alkylphenolic acids and 4 salicylic acid amides, seven of which were new compounds, and tested them for snail killing activity and inhibiting snail climbing activity. The results showed that all alkyl phenolic acids had good snail killing activity. In addition, it was found that phenolic hydroxyl and carboxyl groups were the necessary groups for snail killing activity, and the number of long chain carbon atoms of alkanes also affected the snail killing activity to some extent. The short carbon chain showed stronger snail killing activity and inhibited snail climbing activity, which provided a new idea for us to modify the structure of ginkgo acid and improve the activity of ginkgo acid.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R284;R184
【参考文献】
相关期刊论文 前10条
1 于向民,王文青,吴翠娇,闫凤霞,候颖一;海风藤酮对小鼠抗着床作用的细胞化学和电镜观察[J];青岛医学院学报;1999年01期
2 王庆华;陈敏丽;王晶;翁文;;水杨酸酰胺化衍生物的合成[J];合成化学;2008年02期
3 戴建荣,吴锋,高智慧,洪青标;B002和氯硝柳胺及其复方对鱼类急性毒性的观察[J];实用寄生虫病杂志;1997年04期
4 高智慧,洪青标,戴建荣,周晓农,孙乐平;氯硝柳胺及与五氯酚钠复配后钉螺上爬实验研究[J];实用寄生虫病杂志;1998年03期
5 余书勤，钱之玉;血小板激活因子拮抗剂海风藤酮对人精子体外运动的影响[J];生殖与避孕;1995年01期
6 吴庆立,冯毓秀;五种胡椒属来源的海风藤挥发油成分的比较研究[J];天然产物研究与开发;1994年03期
7 糜留西,张丽红,崔天义,陈伟,刘利铭;灭钉螺植物的筛选[J];武汉植物学研究;1997年04期
8 许义祥,黄社来,陈雪峰,巩六兵;银杏果皮杀灭钉螺的实验研究[J];中国血吸虫病防治杂志;2003年01期
9 奚伟萍,黄轶昕;强螺杀粉剂急性鱼毒实验观察[J];中国血吸虫病防治杂志;2004年01期
10 唐洪杰,张静,董金华,刘百里;水杨酰苯胺类化合物的合成及其抗炎、抗变态反应活性[J];中国药物化学杂志;2000年04期
，本文编号：2120795
本文链接：https://www.wllwen.com/yixuelunwen/liuxingb/2120795.html
