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

The Journal of Antibiotics volume 73, pages 542–547 (2020)Cite this article

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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 Xiao 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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Authors and Affiliations

  1. 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

    Yongxiang Song, Jiafan Yang, Jie Li & Jianhua Ju

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

    Yongxiang Song, Jiafan Yang, Jie Li & Jianhua Ju

  3. Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, 510080, China

    Jianchen Yu & Jie Yuan

  4. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Jianchen Yu & Jie Yuan

  5. National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, The Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, 518020, China

    Nai-Kei Wong

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  1. Yongxiang Song
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Correspondence to Jianhua Ju.

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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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