發(fā)布時(shí)間：2018-07-13 21:29

【摘要】： 血吸蟲病是一種嚴(yán)重危害人類健康和社會(huì)經(jīng)濟(jì)發(fā)展的重大傳染性疾病。我國(guó)流行的是日本血吸蟲病,近幾年來疫情呈明顯上升趨勢(shì)。水陸兩棲湖北釘螺(釘螺)是日本血吸蟲的唯一中間宿主,控制釘螺是血吸蟲病防治的關(guān)鍵技術(shù)之一。國(guó)家需求高效、低毒、價(jià)廉的新型滅螺藥物替代化學(xué)合成的氯硝柳胺。很多植物都有一定的殺滅釘螺的作用,銀杏外果皮的主要成分之一銀杏酸顯示了較強(qiáng)的滅螺活性。 銀杏酸是銀杏外果皮提取物的主要成分,也存在于銀杏的果實(shí)和葉子中,是一類烷基或烯基酚酸化合物。已有研究表明其有較強(qiáng)的殺滅釘螺的作用,具有開發(fā)成高效、低毒、價(jià)廉的新型滅螺藥物的潛力。我們擬合成一系列烷基酚酸,通過包括1)改變烷烴長(zhǎng)鏈在酚酸母核上的位置;2)改變烷烴長(zhǎng)鏈碳原子的數(shù)目等方法探討不同結(jié)構(gòu)的烷基酚酸與其滅螺活性的構(gòu)效關(guān)系。同時(shí),合成一系列具有氯硝柳胺類似結(jié)構(gòu)的化合物,研究其構(gòu)效關(guān)系,尋求一種新的對(duì)化合物的改造途徑以改進(jìn)化合物的滅螺活性。 最終我們合成了6個(gè)烷基酚酸和4個(gè)水楊酸酰胺,其中七個(gè)為新化合物,并對(duì)它們進(jìn)行了滅螺活性和抑制釘螺上爬活性測(cè)試。結(jié)果顯示,所合成的烷基酚酸均具有較好的滅螺活性。而且,通過不同化合物滅螺活性比較發(fā)現(xiàn),酚羥基和羧基是其滅螺活性的必需基團(tuán),而烷烴長(zhǎng)鏈碳原子的數(shù)目也在一定程度上影響其滅螺活性,在以上合成的烷基酚酸中,較短的碳鏈顯示出了較強(qiáng)的滅螺活性和抑制釘螺上爬活性,為我們改造銀杏酸結(jié)構(gòu)、提高銀杏酸滅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.
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R284;R184

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