海绵共附生链霉菌Streptomyces parvulus 162432次级代谢产物研究  

Secondary metabolites of a marine sponge associated Streptomyces parvulus 162432

作　　者：陈瑞强 罗祥超 林厚文 焦伟华[2] CHEN Rui-qiang;LUO Xiang-chao;LIN Hou-wen;JIAO Wei-hua(College of Food,Shanghai Ocean University,Shanghai 201306,China;Research Center for Marine Drugs,State Key Laboratory of Oncogenes and Related Genes,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,China)

机构地区：[1]上海海洋大学食品学院,上海201306 [2]癌基因与相关基因国家重点实验室海洋药物研究中心,上海交通大学医学院附属仁济医院,上海200127

出　　处：《中草药》2023年第13期4104-4110,共7页Chinese Traditional and Herbal Drugs

基　　金：国家重点研发计划项目(2022YFC2804100);国家自然科学基金项目(22137006);国家自然科学基金项目(82022068)。

摘　　要：目的研究海绵共附生链霉菌Streptomyces parvulus162432的化学成分。方法采用十八烷基硅烷键合硅胶填料(ODS)中压柱色谱和半制备高效液相色谱等技术进行分离纯化,得到的单体化合物采用HR-ESI-MS、NMR以及文献比对等方法进行鉴定,新化合物的绝对构型通过计算NMR和圆二色谱(ECD)确定。结果从菌株Streptomyces parvulus 162432中分离纯化了9个环二肽类化合物,包括1个新化合物链霉菌二肽A(1)和8个已知化合物:环-(D-顺式-羟脯氨酸-L-苯丙氨酸)(2)、环-(D-脯氨酸-D-苯丙氨酸)(3)、环-(L-羟脯氨酸-L-亮氨酸)(4)、环-(L-羟脯氨酸-D-亮氨酸)(5)、环-(D-脯氨酸-L-亮氨酸)(6)、环-(L-脯氨酸-D-亮氨酸)(7)、环-(D-脯氨酸-L-异亮氨酸)(8)、环-(L-亮氨酸-D-缬氨酸)(9)。对分离得到的化合物1~9进行肿瘤细胞增殖细胞毒和抗菌活性评价,活性结果显示,化合物1~9在10μg/mL下对肿瘤细胞增殖均未显示出明显的细胞毒活性;化合物9对苏云金芽孢杆菌显示抑菌活性,最小抑菌浓度(minimum inhibitory concentration,MIC)为25μg/mL。结论化合物1为新化合物,化合物2和4~9为首次从链霉菌Streptomyces parvulus中分离得到,化合物9具有一定的抗菌活性。Objective To reveal the secondary metabolites of a marine sponge associated Streptomycesparvulus 162432.Methods The organic extract and fractions were separated and purified by octadecylsilyl silica(ODS)medium-pressure column chromatography(MPLC)and semi-preparative high-performance liquid chromatography(HPLC).The obtained purified compounds were identified by high-resolution-electrospray-mass spectrometry(HR-ESI-MS),nuclear magnetic resonance spectroscopy(NMR)andliterature data comparison.The absolute configuration of new compound was determined by NMR and electrostatic circular dichroism(ECD)calculations.Results Nine compounds were isolated from S.parvulus 162432,including one new compound streptomyces dipeptide A(1)and eight known compounds:cyclo-(D-cis-Hyp-L-Phe)(2),cyclo-(D-Pro-D-Phe)(3),cyclo-(L-Hyp-L-Leu)(4),cyclo-(L-Hyp-D-Leu)(5),cyclo-(D-Pro-L-Leu)(6),cyclo-(L-Pro-D-Leu)(7),cyclo-(D-Pro-L-Ile)(8),cyclo-(L-Leu-D-Val)(9).The cytotoxicityon tumor cellproliferation and antibacterial activities of the isolated compounds 1-9were evaluated.None of compounds1-9showed significant cytotoxic activity on tumor cell proliferation at the concentration of 10µg/mL;compound 9 showed antibacterial activity against Bacillus thuringiensiswith the minimal inhibitory concentration(MIC)value of 25µg/mL.Conclusion Compound 1 is a new compound,compound 2 and 4-9 are isolated from S.parvulusfor the first time.Compound 9 showed antibacterialactivity against B.thuringiensis.

关 键 词：海绵 链霉菌Streptomyces parvulus 162432 链霉菌二肽A 环-(L-亮氨酸-D-缬氨酸) 海洋天然产物 抗菌活性 

分 类 号：R284.1[医药卫生—中药学]