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New peptidendrocins and anticancer chartreusin from an endophytic bacterium of Dendrobium officinale

Huimin ZhaoJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaXiabin ChenKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaXiaoling ChenKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaYoujuan ZhuJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaYichao KongKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaSifang ZhangJiangsu Health Vocational College, Nanjing 211800, ChinaXingyu DengKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaPengfei OuyangKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaWei ZhangKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaShurong HouKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, ChinaXiachang WangJiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaTian XieKey Laboratory of Elemene Class Anti-Cancer Chinese Medicine of Zhejiang Province, Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Holistic Integrative Pharmacy Institutes (HIPI), School of Medicine, Hangzhou Normal University, Hangzhou 311121, China
2020en
ABI

Abstract

Background: Endophyte has now become a potential source for the discovery of novel natural products, as they participate in biochemical pathways of their hosts and produce analogous or novel bioactive compounds. As an epiphytic plant, Dendrobium officinale is one of precious Chinese medicines with various activities. It is well known for containing diverse endophytes, but so far not much is known about their secondary metabolites. Methods: the plant tissues were cut and cultured on agar plates to isolate and purify the endophytic bacteria from Dendrobium officinale. Taxonomical identification of strains was performed by 16s rRNA. At the same time, the crude extracts of the strains were tested for antibacterial and cytotoxic activities to screen out one endophyte, Streptomyces sp. SH-1.2-R-15 for further study. After scale-up fermentation, isolation, purification and structure elucidation by using MS, 1D/2D-NMR spectroscopic method, secondary metabolites were identified and submitted for biological activity test. Results: Fifty-eight endophytic strains representing 9 genera were obtained, with 50% of strains were Streptomyces. One of the most active strain, Streptomyces sp. 1.2-R-15, was selected for bioassay-guided isolation, which led to the discovery of two new peptide-type compounds 1 and 2, as well as a bioactive chartreusin, and four other known natural products. Their structures were determined by comprehensive spectroscopic techniques. Chartreusin showed potent cytotoxicity against Hep3B2.1-7 (IC50 =18.19 µM) and H1299 (IC50 =19.74 µM) cancer cell lines, and antibacterial activity against S. aureus (IC50 =23.25 µM). Conclusions: This study highlights the endophytic bacteria from medical plant D. officinale have potential bioactivity and natural product diversity, thus implicates them as a valuable source for new anticancer and antibiotics agents.

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