【摘要】：膠質(zhì)瘤是目前最常見(jiàn)和最惡性的腦腫瘤,由于其位于大腦功能區(qū)使得手術(shù)切除極為困難,化療在治療膠質(zhì)瘤的過(guò)程中尤其重要。但現(xiàn)有抗膠質(zhì)瘤藥物難以滿足臨床的需求,迫切需要研發(fā)新型抗膠質(zhì)瘤藥物。海洋天然產(chǎn)物尤其是海洋細(xì)菌來(lái)源的天然產(chǎn)物是抗腫瘤新藥或先導(dǎo)化合物的源泉。本論文從4個(gè)海洋樣品中分離得到42株海洋細(xì)菌,發(fā)現(xiàn)了具有抗膠質(zhì)瘤活性的14株菌株,并對(duì)其中兩株活性菌株的化學(xué)成分及其抗膠質(zhì)瘤活性進(jìn)行了研究,總計(jì)分離鑒定了 17個(gè)化合物,發(fā)現(xiàn)了 7個(gè)結(jié)構(gòu)新穎的新化合物。從鏈霉菌Streptomyces sp.ZQ4BG中分離到10個(gè)化合物(1-10),包括7個(gè)新的多烯多羥基大環(huán)內(nèi)酯類化合物黃色真菌素Ⅲ-Ⅸ(Ⅲ-Ⅸ,3-9)和已知化合物黃色真菌素Ⅰ(1)、Ⅱ(2)和spectinabilin(10)。這些化合物的化學(xué)結(jié)構(gòu)是通過(guò)NMR、HRESIMS波譜分析、對(duì)比Kishi's 13CUniversalNMR數(shù)據(jù)庫(kù)、丙叉反應(yīng)和Mosher反應(yīng)等多種方法相結(jié)合而確定的。新化合物黃色真菌素Ⅳ-Ⅷ(4-8)含有一個(gè)罕見(jiàn)的四氫呋喃環(huán),而黃色真菌素Ⅸ(9)是目前發(fā)現(xiàn)的第一個(gè)含有環(huán)氧七元環(huán)的多烯多羥基大環(huán)內(nèi)酯。新的黃色真菌素Ⅲ-Ⅸ(3-9)推測(cè)由已知的黃色真菌素Ⅰ(1)和Ⅱ(2)衍生而來(lái)。生物活性研究表明,黃色真菌素Ⅰ(1)、Ⅱ(2)和spectinabilin(10)對(duì)膠質(zhì)瘤細(xì)胞的增殖和白色念珠菌的生長(zhǎng)均有一定的抑制作用,但新化合物黃色真菌素Ⅲ-Ⅸ(3-9)沒(méi)有顯示較好的生物活性。從細(xì)菌ZQ5-21B中分離并鑒定了 7個(gè)已知化合物,它們是2'-鳥(niǎo)嘌呤脫氧核苷(11)、2'-腺嘌呤脫氧核苷(12)、腺嘌呤核苷(13)、2'-胸腺嘧啶脫氧核苷(14)、2'-尿嘧啶脫氧核苷(15)、尿嘧啶核苷(16)和3,4-二甲氧基肉桂酸(17)。這些核苷化合物并沒(méi)有發(fā)現(xiàn)具有抗膠質(zhì)瘤活性。本論文從海洋細(xì)菌ZQ4BG中發(fā)現(xiàn)了一系列結(jié)構(gòu)獨(dú)特而少見(jiàn)的多烯多羥基大環(huán)內(nèi)酯類新化合物,并用多種方法相結(jié)合成功鑒定了它們的化學(xué)結(jié)構(gòu),極大地豐富了這類化合物的結(jié)構(gòu)多樣性,并首次報(bào)道了黃色真菌素Ⅰ(1)、Ⅱ(2)和spectinabilin(10)的抗膠質(zhì)瘤活性。
[Abstract]:Glioma is the most common and malignant brain tumor at present, because of its location in the brain functional area, surgical resection is extremely difficult, chemotherapy is particularly important in the treatment of glioma. However, the existing anti-glioma drugs are difficult to meet the clinical needs, so it is urgent to develop new anti-glioma drugs. Marine natural products, especially those derived from marine bacteria, are the source of new anti-tumor drugs or lead compounds. In this paper, 42 strains of marine bacteria were isolated from 4 marine samples, and 14 strains with anti-glioma activity were found, and the chemical constituents and anti-glioma activity of two of them were studied. A total of 17 compounds were isolated and identified, and 7 novel compounds were found. Ten compounds (1-10) were isolated from Streptomyces sp.ZQ4BG, including seven new polyhydroxy macrolides, xanthophyllins 鈪，

本文編號(hào)：2420863