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 IC50 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.
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Acknowledgements
This study was supported, in part, by the Program of Guangzhou Science and Technology Plan (201707010454), the National Natural Science Foundation of China (41676151), Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) (GML2019ZD0406), the National Key Research and Development Program of China (2017YFD0201401) and the Special Fund for Strategic Pilot Technology of Chinese Academy of Sciences (XDA13020302-2). We thank the analytical facility center of the South China Sea Institute of Oceanology, Dr. Zhihui **ao and Mr. Chuanrong Li for recording NMR data and Ms. Aijun Sun, and Ms. Yun Zhang for acquisition of ESIMS and HRESIMS data. Additionally, we appreciate Professor Jianhua Liu from South China Agricultural University and our colleague Professor Chang Chen for their gift of pathogenic bacteria MRSA GDQ6P012P and GDE4P037P and four Vibrio sp. strains, respectively.
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Dedicated to Professor William Fenical in recognition of his contributions to marine derived secondary metabolites.
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Song, Y., Yang, J., Yu, J. et al. Chlorinated bis-indole alkaloids from deep-sea derived Streptomyces sp. SCSIO 11791 with antibacterial and cytotoxic activities. J Antibiot 73, 542–547 (2020). https://doi.org/10.1038/s41429-020-0307-4
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DOI: https://doi.org/10.1038/s41429-020-0307-4
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