Chlorinated bis-indole alkaloids from deep-sea derived Streptomyces sp. SCSIO 11791 with antibacterial and cytotoxic activities
Chlorinated bis-indole alkaloids from deep-sea derived Streptomyces sp. SCSIO 11791 with antibacterial and cytotoxic activities
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来自深海链霉菌的氯化双吲哚生物碱。
DOI：
10.1038/s41429-020-0307-4
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发表时间：
2020-04-24
影响因子：
3.3
通讯作者：
Ju, Jianhua
中科院分区：
文献类型：
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作者：
Song, Yongxiang;Yang, Jiafan;Ju, Jianhua
从深海来源的链霉菌SCSIO 11791中分离得到两个新的氯代双吲哚生物碱：迪奥霉素（1）和6-OMe-7 '，7“-二氯色吡咯酸（2），以及沿着7个已知的类似物3-9。通过大量的HRESIMS和1D和2D NMR数据分析，确定了它们的结构。体外抗菌和细胞毒性试验表明，化合物1对6株临床分离自人和猪的耐甲氧西林金黄色葡萄球菌（MRSA）显示出抗葡萄球菌活性，MIC范围为1-2 μ g/mL。此外，化合物1显示出对人癌细胞系NCI-H460、MDA-MB-231、HCT-116、HepG 2和非癌性MCF 10A的细胞毒活性，IC 50范围为3.1-11.2 μ M。构效关系分析表明，C-6“位的氯原子可能是影响其生物活性的关键，从而为药物设计中对双吲哚生物碱骨架进行化学修饰提供了线索。
Two new chlorinated bis-indole alkaloids, dionemycin (1) and 6-OMe-7 ',7 ''-dichorochromopyrrolic acid (2), along with seven known analogs 3-9, were isolated from the deep-sea derived Streptomyces sp. SCSIO 11791. Their structures were elucidated by extensive HRESIMS, and 1D and 2D NMR data analysis. In vitro antibacterial and cytotoxic assays revealed that, compound 1, shows anti-staphylococcal activity with an MIC range of 1-2 mu g/mL against six clinic strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from human and pig. Additionally, compound 1 displayed cytotoxic activity against human cancer cell lines NCI-H460, MDA-MB-231, HCT-116, HepG2, and noncancerous MCF10A with an IC50 range of 3.1-11.2 mu M. Analysis of the structure-activity relationship reveals that the chlorine atom at C-6 '' could be pivotal for conferring their bioactivities, thus providing hints on chemical modifications on bis-indole alkaloid scaffold in drug design.