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Targeted isolation of sulfur-containing metabolites from Lsr2-deletion mutant strain of Streptomyces roseosporus

机译:迷迭香链霉菌 Lsr2 缺失突变菌株的目标硫分离代谢

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Deletion of the Lsr2 gene in Streptomyces roseosporus up-regulated silent gene clusters and produced new secondary metabolites. An ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF-MS/MS) method was used to analyze metabolites of the mutant and wild-type strains, and recognize previously unreported sulfur-containing compounds based on their molecular formulas and fragmentation ions. The targeted isolation of unidentified compounds afforded six new sulfur-containing compounds, pyrismycins A–F (1–6), together with seven known analogues 7–13. Their cytotoxic effects were evaluated using four clinically relevant human cancer cell lines, gastric carcinoma SGC7901, breast carcinoma MDA-MB-231, lung carcinoma A549 and hepatocellular carcinoma HepG2. Compound 7 exhibited the most potent cytotoxicity with IC50 values of 1.7, 5.8 and 6.3 μM against the SGC7901, HepG2 and MDA-MB-231, respectively.
机译:玫瑰链霉菌 Lsr2 基因的缺失上调沉默基因簇并产生新的次生代谢产物。使用超高效液相色谱四极杆飞行时间质谱(UPLC-QTOF-MS / MS)方法分析突变菌株和野生型菌株的代谢产物,并根据其分子式和分子式识别先前未报告的含硫化合物。碎片离子。通过对未鉴定化合物的靶向分离,得到了六种新的含硫化合物,嘧菌霉素A-F(1-6),以及七种已知的类似物7-13。使用四种临床相关的人类癌细胞系胃癌SGC7901,乳腺癌MDA-MB-231,肺癌A549和肝细胞癌HepG2评估了它们的细胞毒性作用。化合物7对SGC7901,HepG2和MDA-MB-231表现出最强的细胞毒性,IC 50 值分别为1.7、5.8和6.3μM。

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