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

• Published in: Journal of antibiotics Vol. 73; no. 8; pp. 542 - 547
• Main Authors: Song, Yongxiang, Yang, Jiafan, Yu, Jianchen, Li, Jie, Yuan, Jie, Wong, Nai-Kei, Ju, Jianhua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2020; Springer Nature; Nature Publishing Group
• Subjects: 631/92/349; 631/92/613; Animals; Aquatic Organisms - chemistry; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Biotechnology & Applied Microbiology; Cell Line; Cell Line, Tumor; Chlorine; Cytotoxicity; Cytotoxins - chemistry; Cytotoxins - pharmacology; Deep sea; HCT116 Cells; Hep G2 Cells; Humans; Immunology; Indole Alkaloids - chemistry; Indole Alkaloids - pharmacology; Life Sciences; Life Sciences & Biomedicine; Medicinal Chemistry; Microbial Sensitivity Tests; Microbiology; Organic Chemistry; Pharmacology & Pharmacy; Science & Technology; Special Feature: Article; Staphylococcus infections; Streptomyces - chemistry; Swine; BISINDOLE ALKALOIDS; A-E; INHIBITORS; ANALOGS; REBECCAMYCIN
• ISSN: 0021-8820; 1881-1469; 1881-1469
• DOI: 10.1038/s41429-020-0307-4

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 50 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.