本文關(guān)鍵詞：四株內(nèi)生真菌和一種植物的化學(xué)成分及其生物活性研究　出處：《山東大學(xué)》2017年博士論文　論文類(lèi)型：學(xué)位論文

  更多相關(guān)文章： 苔蘚內(nèi)生真菌 地衣內(nèi)生真菌 向天果 次生代謝產(chǎn)物 結(jié)構(gòu)解析 生物活性

【摘要】：植物內(nèi)生真菌(Endophytic fungi)是指一類(lèi)在一定階段或全部階段均生活在健康的組織和器官內(nèi)部,而不使宿主表現(xiàn)出明顯病害癥狀的真菌。并且在與宿主長(zhǎng)期協(xié)同進(jìn)化的過(guò)程中,它們產(chǎn)生了許多活性?xún)?yōu)異和結(jié)構(gòu)新穎的次生代謝產(chǎn)物,受到了天然產(chǎn)物化學(xué)家們的關(guān)注。植物內(nèi)生真菌作為豐富的真菌基因多樣性寶庫(kù),為人們發(fā)現(xiàn)可持續(xù)的、結(jié)構(gòu)新穎和活性多樣的先導(dǎo)化合物提供了重要來(lái)源。所以針對(duì)一些特殊群體(如以苔蘚和地衣為宿主)內(nèi)生真菌的次生代謝產(chǎn)物研究具有重大的意義。本文對(duì)四株植物內(nèi)生真菌(包括一株苔蘚內(nèi)生真菌和三株地衣內(nèi)生真菌)和一種傳統(tǒng)藥物植物向天果的化學(xué)成分進(jìn)行了系統(tǒng)研究。根據(jù)前期活性篩選的結(jié)果選擇 了 Aspergillus fumigatus、Phialocephala fortinii、Phaeosphaeria avenariaf sp.和Ulospwra bilgamii這四株內(nèi)生真菌使用大米培養(yǎng)基進(jìn)行放大發(fā)酵。分別使用乙酸乙酯和甲醇對(duì)菌株發(fā)酵產(chǎn)物和向天果進(jìn)行提取,采用硅膠柱色譜、葡聚糖凝膠Sephadex LH-20柱色譜、ODS柱色譜以及高效液相柱色譜等多種分離純化技術(shù),從四株內(nèi)生真菌和一種植物中共分離得到78個(gè)化合物,其中包括32個(gè)新化合物。綜合采用質(zhì)譜、核磁共振、單晶衍射和圓二色譜等方法確定了化合物的平面結(jié)構(gòu)和立體構(gòu)型。對(duì)分得的化合物進(jìn)行細(xì)胞毒、抗真菌和α-葡萄糖苷酶抑制等活性評(píng)價(jià),結(jié)果顯示部分化合物具有顯著的活性,其中化合物25和30與氟康唑聯(lián)用具有很好的逆轉(zhuǎn)耐藥活性。進(jìn)一步活性機(jī)制研究表明,化合物25和30通過(guò)抑制基因MDR1的表達(dá)來(lái)抑制外排泵的活性,進(jìn)而實(shí)現(xiàn)逆轉(zhuǎn)耐藥。
[Abstract]:Endophytic fungi is a kind of fungus that lives in healthy tissues and organs at a certain stage or at all stages, but does not make the host show obvious symptoms of disease. And in the process of long-term co evolution with host, they have produced many secondary metabolites with excellent activity and novel structure, which have attracted the attention of natural product chemists. Endophytic fungi, as a rich repository of fungal diversity, provide an important source for finding sustainable, novel and active lead compounds. Therefore, it is of great significance to study the secondary metabolites of endophytic fungi, such as moss and lichens. The chemical constituents of four endophytic fungi, including a bryophyte endophytic fungus and three lichen endophytic fungi, and a traditional medicinal plant, "Tian Tian Guo", were systematically studied in this paper. According to the results of previous active screening, four endophytic fungi, including Aspergillus fumigatus, Phialocephala fortinii, Phaeosphaeria avenariaf sp. and Ulospwra bilgamii, were selected for amplification and fermentation using rice medium. The fermentation products were extracted and used to fruit ethyl acetate and methanol, separation and purification by silica gel column chromatography, Sephadex Sephadex column chromatography, LH-20 ODS column chromatography and high performance liquid chromatography and other fungi, and a plant in a total of 78 compounds were isolated from four strains, including 32 new compounds. The plane structure and stereotyping of the compounds were determined by mass spectrometry, nuclear magnetic resonance, single crystal diffraction and circular two chromatography. The activity of the obtained compounds was evaluated by cytotoxic, antifungal and alpha glucosidase activities. The results showed that some compounds had significant activity. Compound 25 and 30 combined with fluconazole had a good reversal of drug resistance. Further studies have shown that compounds 25 and 30 inhibit the activity of the efflux pump by inhibiting the expression of gene MDR1 and then reverse the drug resistance.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R284

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本文編號(hào)：1340449