海洋细菌ZQ4BG和ZQ5-21B抗胶质瘤活性成分的研究

发布时间：2019-02-12 22:39

【摘要】：胶质瘤是目前最常见和最恶性的脑肿瘤,由于其位于大脑功能区使得手术切除极为困难,化疗在治疗胶质瘤的过程中尤其重要。但现有抗胶质瘤药物难以满足临床的需求,迫切需要研发新型抗胶质瘤药物。海洋天然产物尤其是海洋细菌来源的天然产物是抗肿瘤新药或先导化合物的源泉。本论文从4个海洋样品中分离得到42株海洋细菌,发现了具有抗胶质瘤活性的14株菌株,并对其中两株活性菌株的化学成分及其抗胶质瘤活性进行了研究,总计分离鉴定了 17个化合物,发现了 7个结构新颖的新化合物。从链霉菌Streptomyces sp.ZQ4BG中分离到10个化合物(1-10),包括7个新的多烯多羟基大环内酯类化合物黄色真菌素Ⅲ-Ⅸ(Ⅲ-Ⅸ,3-9)和已知化合物黄色真菌素Ⅰ(1)、Ⅱ(2)和spectinabilin(10)。这些化合物的化学结构是通过NMR、HRESIMS波谱分析、对比Kishi's 13CUniversalNMR数据库、丙叉反应和Mosher反应等多种方法相结合而确定的。新化合物黄色真菌素Ⅳ-Ⅷ(4-8)含有一个罕见的四氢呋喃环,而黄色真菌素Ⅸ(9)是目前发现的第一个含有环氧七元环的多烯多羟基大环内酯。新的黄色真菌素Ⅲ-Ⅸ(3-9)推测由已知的黄色真菌素Ⅰ(1)和Ⅱ(2)衍生而来。生物活性研究表明,黄色真菌素Ⅰ(1)、Ⅱ(2)和spectinabilin(10)对胶质瘤细胞的增殖和白色念珠菌的生长均有一定的抑制作用,但新化合物黄色真菌素Ⅲ-Ⅸ(3-9)没有显示较好的生物活性。从细菌ZQ5-21B中分离并鉴定了 7个已知化合物,它们是2'-鸟嘌呤脱氧核苷(11)、2'-腺嘌呤脱氧核苷(12)、腺嘌呤核苷(13)、2'-胸腺嘧啶脱氧核苷(14)、2'-尿嘧啶脱氧核苷(15)、尿嘧啶核苷(16)和3,4-二甲氧基肉桂酸(17)。这些核苷化合物并没有发现具有抗胶质瘤活性。本论文从海洋细菌ZQ4BG中发现了一系列结构独特而少见的多烯多羟基大环内酯类新化合物,并用多种方法相结合成功鉴定了它们的化学结构,极大地丰富了这类化合物的结构多样性,并首次报道了黄色真菌素Ⅰ(1)、Ⅱ(2)和spectinabilin(10)的抗胶质瘤活性。
[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，

本文编号：2420863