三株海洋细菌抗胶洗质瘤活性成分的研究-海洋科学专业毕业论文.docx

浙江大学硕士学位论文 摘要 摘要 胶质瘤是人类最恶性的脑肿瘤之一，而现有的化疗药物及治疗手段并不能满 足要求，迫切需要研究开发新的抗胶质瘤药物；天然产物尤其是海洋天然产物是 新药或新药先导化合物的重要宝库。本文研究了海洋细菌链霉菌Streptomyces sp． 182SMLY和两株未鉴定的菌株(ZQ4-23和P81-A)的化学成分及它们的抗胶质瘤 活性。从三株海洋细菌中共分离得到11个化合物(以下简称化合物1～11)，其 中从菌株Streptomyces sp．182SMLY中分离鉴定了八个化合物，包括五个为新化 合物。新化合物的结构是通过一维和二维的NMR波谱、高分辨质谱和ECD计算 等多种方法而鉴定的，它们是蒽醌类化合物N—acetyl-N-demethylmayamycin(1) 和streptoanthraquinone A(2)以及吩嗪类化合物O-streptophenazine M(3)、 ㈠-streptophenazine N(5)和(_)-streptophenazine O(7)。新化合物 streptoanthraquinoneA具有较为独特的结构。从菌株ZQ4_23中分离鉴定了两个同 分异构的肉桂酸类已知化合物(9，10)，并从菌株P81．A中分离得到已知化合物 2．甲基苯甲酸(11)。 生物活性研究发现，两个蒽醌类新化合物N-acetyl-N．demethylmayamycin(1) 和streptoanthraquinone A(2)显著抑制四种不同胶质瘤细胞的增殖并诱导胶质瘤 细胞凋亡。进一步研究发现N-acetyl-N-demethylmayamycin(1)影响胶质瘤细胞 糖酵解途径代谢酶磷酸果糖激酶PFKFB3的蛋白表达水平，提示N．acetyl-N． demethylmayamycin(1)抗胶质瘤的作用机制之一可能与肿瘤细胞代谢有关。 关键词：胶质瘤、海洋细菌、菌株Streptomyces sp．182SMLY、菌株ZQ4．23、菌 株P81-A、新蒽醌类化合物、新吩嗪类化合物、胶质瘤细胞增殖、胶质瘤细胞凋 亡、胶质瘤细胞代谢酶 II 万方数据  浙江大学硕士学位论文 摘要 ABSTRACT Gliomas are one of the most malignant brain tumors．The current chemotherapy and treated strategy are not satisfactory．There is therefore a need to develop novel anti-glioma agents for treating malignant gliomas．Natural products especially marine natural products are highly significant sources of drug leads．In this thesis，the chemical constituents from marine bacteria Streptomyces sp．strain 1 82SMLY and two unidentified strains ZQ4-23 and P8 1·A were investigated．The activity of the isolated compounds from the three bacteria against the proliferation of different glioma cells was also evaluated．A total of 1 1 constituents including five new compounds were obtained in this study．Based on the analyses of the NMR and HRESIMS data as well as the ECD calculation，these new compounds were determined as N-acetyl-N—demethylmayamycin、streptoanthraquinone A、O—streptophenazine M、 O—streptophenazine N，and(--)-streptophenazine O．