深海来源链霉菌 SCSIO 11791 中具有抗菌和细胞毒性的氯化双吲哚生物碱。

Chlorinated bis-indole alkaloids from deep-sea derived Streptomyces sp. SCSIO 11791 with antibacterial and cytotoxic activities.

机构信息

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou, 510301, China.

College of Oceanology, University of Chinese Academy of Sciences, 19 Yuquan Road, Beijing, 100049, China.

出版信息

J Antibiot (Tokyo). 2020 Aug;73(8):542-547. doi: 10.1038/s41429-020-0307-4. Epub 2020 Apr 24.

DOI:10.1038/s41429-020-0307-4

PMID:32332871

Abstract

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 μg/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 IC range of 3.1-11.2 μM. 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.

摘要

从深海来源的链霉菌 SCSIO 11791 中分离得到两种新的氯化双吲哚生物碱，即地奥霉素（1）和 6-OMe-7'，7″-二氯色吡咯酸（2），以及 7 种已知类似物 3-9。通过扩展的 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 对从人和猪中分离的 6 株耐甲氧西林金黄色葡萄球菌（MRSA）的临床分离株具有抗葡萄球菌活性，MIC 范围为 1-2μg/mL。此外，化合物 1 对人癌细胞系 NCI-H460、MDA-MB-231、HCT-116、HepG2 和非癌细胞系 MCF10A 显示出细胞毒性活性，IC 范围为 3.1-11.2μM。构效关系分析表明，C-6″位的氯原子可能对赋予它们的生物活性至关重要，从而为双吲哚生物碱骨架的药物设计提供了化学修饰的线索。