【摘要】： 血吸蟲(chóng)病是一種嚴(yán)重危害人類(lèi)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(chóng)病,近幾年來(lái)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(chóng)的唯一中間宿主,控制釘螺是血吸蟲(chóng)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(lèi)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(kāi)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(guò)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(lèi)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(guò)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(lèi)號(hào)】：R284;R184

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 于向民,王文青,吳翠嬌,閆鳳霞,候穎一;海風(fēng)藤酮對(duì)小鼠抗著床作用的細(xì)胞化學(xué)和電鏡觀察[J];青島醫(yī)學(xué)院學(xué)報(bào);1999年01期

2 王慶華;陳敏麗;王晶;翁文;;水楊酸酰胺化衍生物的合成[J];合成化學(xué);2008年02期

3 戴建榮,吳鋒,高智慧,洪青標(biāo);B002和氯硝柳胺及其復(fù)方對(duì)魚(yú)類(lèi)急性毒性的觀察[J];實(shí)用寄生蟲(chóng)病雜志;1997年04期

4 高智慧,洪青標(biāo),戴建榮,周曉農(nóng),孫樂(lè)平;氯硝柳胺及與五氯酚鈉復(fù)配后釘螺上爬實(shí)驗(yàn)研究[J];實(shí)用寄生蟲(chóng)病雜志;1998年03期

5 余書(shū)勤，錢(qián)之玉;血小板激活因子拮抗劑海風(fēng)藤酮對(duì)人精子體外運(yùn)動(dòng)的影響[J];生殖與避孕;1995年01期

6 吳慶立,馮毓秀;五種胡椒屬來(lái)源的海風(fēng)藤揮發(fā)油成分的比較研究[J];天然產(chǎn)物研究與開(kāi)發(fā);1994年03期

7 糜留西,張麗紅,崔天義,陳偉,劉利銘;滅釘螺植物的篩選[J];武漢植物學(xué)研究;1997年04期

8 許義祥,黃社來(lái),陳雪峰,鞏六兵;銀杏果皮殺滅釘螺的實(shí)驗(yàn)研究[J];中國(guó)血吸蟲(chóng)病防治雜志;2003年01期

9 奚偉萍,黃軼昕;強(qiáng)螺殺粉劑急性魚(yú)毒實(shí)驗(yàn)觀察[J];中國(guó)血吸蟲(chóng)病防治雜志;2004年01期

10 唐洪杰,張靜,董金華,劉百里;水楊酰苯胺類(lèi)化合物的合成及其抗炎、抗變態(tài)反應(yīng)活性[J];中國(guó)藥物化學(xué)雜志;2000年04期

，

本文編號(hào)：2120795