【作者】 马菁菁；

【导师】 周光雄； 高昊； 唐金山；

【作者基本信息】 暨南大学 ， 药物化学， 2010， 硕士

【摘要】 本论文对两株初筛分别具有互动抗真菌活性和HCT-116细胞毒活性的海洋放线菌No. Ms252、No.172221的发酵液进行活性跟踪分离和结构鉴定。利用硅胶柱开放柱色谱、ODS开放柱色谱、制备型HPLC等多种色谱方法,从活性流分中分离得到15个化合物,通过现代波谱学手段(MS、1D及2D-NMR)鉴定了它们的结构,分别为：3,3-二(3′-吲哚基)-1,2丙二醇(化合物1)、星孢菌素苷(化合物2)、5-9H-吡啶并[3,4-b]吲哚基-2-呋喃甲醇(化合物3)、1-[5-(羟基甲基)-2-呋喃基]-9H-吡啶并[3,4-b]吲哚基-3-羧酸(化合物4)、麦角甾-3β，5α,6β-三醇(化合物5)、麦角甾-3β,5α,6β-三醇-βD-葡萄糖苷(化合物6)、β-胡萝卜苷(化合物7)、环(脯-亮)二肽(化合物8)、环(脯-缬)二肽(化合物9)、脯氨酸(化合物10)、十六烷酸(化合物11)、N-苯甲基氨基甲酸(化合物12)、1,3-丙二醇苯乙酸酯(化合物13)、大豆素(化合物14)、腺嘌呤核苷(化合物15)。其中,化合物1～4为吲哚类生物碱,化合物5～7为甾体类化合物,化合物8～9为放线菌常见的代谢产物环二肽类化合物。化合物1、3-4和6为首次从放线菌中分离得到,化合物12～13为新天然产物。通过合作单位对所分离的单体进行活性评价,发现化合物1～4表现出一定抗真菌活性,但无显著互动活性；化合物5～11对HCT-116细胞毒活性较弱。更多还原

【Abstract】 This thesis has studied on the bioactive-guided isolation and structural determination of active constituents in fermentation broth from two strains of marine actinomycetes No. Ms252 and No.172221 that respectively showed antifungal effect and synergistic antifungal effect and cytotoxic activity for HCT-116 in early screening. Fifteen compounds were isolated from the active fractions by silica gel column, ODS open column chromatography, preparative HPLC and other chromatographic techniques. Their structures were identified as 3,3-bis(3’-indolyl)-1,2-propanediol (1), staurosporine aglycon (2),5-(9H-pyrido[3,4-b]indol-1-yl)-2-furanmethanol (3), 1-[5-(hydroxymethyl)-2-furanyl]-9H-Pyrido[3,4-b]inddole-3-carboxylic acid (4), methylcholestane-3β,5α,6β-triol (5), ergostane-β-D-glucopyranoside (6),β-daucosterol (7), cyclo-(Pro-Leu) (8), cyclo-(Pro-Val) (9), proline (10), palmitic acid (11), N-(phenylmethyl)-carbamic acid(12),1,3-propanediyl benzeneacetic acid ester (13), daidzein (14) and adenosine (15) by modern spectroscopic methods (MS, 1D and 2D-NMR). Among them, compounds 1～4 are indole alkaloids, compounds 5～7 are steroids, compounds 8～9 are cyclic dipeptides usually seen in the microorganism metabolites, whereas 1,3～4 and 6 was isolated from actinomycete for the first time. Compounds 12～13 are new natural products. Then these compounds were evaluated on the activity through co-operations. We found that compounds 1～4 showed certain degree antifungal activity but no significant synergistic effect, compounds 5～15 showed weak cytotoxic activity for HCT-116.更多还原