title: New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.
abstract: An extract prepared from the culture of a marine-derived actinomyceteStreptomycessp. ZZ338 was found to have significant antimicrobial and antiproliferative activities. A chemical investigation of this active extract resulted in the isolation of three known bioactive actinomycins (1-3) and two new metabolites (4and5). The structures of the isolated compounds were identified as actinomycins D (1), V (2), X0β(3), 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (4), andN-1S-(4-methylaminophenylmethyl)-2-oxo-propyl acetamide (5) based on their nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) data as well as their optical rotation. This class of new compound5had never before been found from a natural resource. Three known actinomycins showed activities in inhibiting the proliferation of glioma cells and the growth of methicillin-resistantStaphylococcus aureus,Escherichia coli, andCandida albicansand are responsible for the activity of the crude extract. Actinomycin D (1) was also found to downregulate several glioma metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis, suggesting that targeting multiple tumor metabolic regulators might be a new anti-glioma mechanism of actinomycin D. This is the first report of such a possible mechanism for the class of actinomycins.
authors.affiliation: Ocean College, Zhejiang University, Zhoushan 316021, China. xiufangzhang623@163.com.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Ocean College, Zhejiang University, Zhoushan 316021, China. moshangmowei@163.com.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Ye
authors.affiliation: Ocean College, Zhejiang University, Zhoushan 316021, China. chaiweiyun@163.com.
authors.forename: Weiyun
authors.initials: W
authors.lastname: Chai
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. xylian@zju.edu.cn.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Lian
authors.affiliation: Ocean College, Zhejiang University, Zhoushan 316021, China. zzhang88@zju.edu.cn.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D003609:Dactinomycin / Q000378:metabolism* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009792:Oceans and Seas; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D003609:Dactinomycin
keywords: actinomycins; antimicrobial activity; antiproliferative activity; glioma cells; glioma metabolic enzymes; marine Streptomyces sp. ZZ338; new metabolites