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The isolation of tetrangomycin from terrestrial Streptomyces sp. CAH29: evaluation of antioxidant, anticancer, and anti-MRSA activity

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Abstract

A rhizosphere isolate Streptomyces sp. CAH29 was found to possess potent antibacterial and antifungal activity against a variety of test organisms. Based on 16S ribosomal ribonucleic acid sequence homology studies, this strain was found to be similar to Streptomyces stramineus (gene sequence similarity 99 %). The major bioactive metabolite produced by Streptomyces sp. CAH29 isolate was extracted, purified andidentified by nuclear magnetic resonance as tetrangomycin. This known anthraquinone-exhibited antimicrobial activity against Staphylococcus aureus, Streptococcus pyogenes, methicillin resistant Staphylococcus aureus and Candida albicans with inhibition zones of 14, 10, 12 and 8 mm, respectively. Docking results demonstrate that tetrangomycin has a similar mode of action and a comparable docking score to bind to the dehydrosqualene synthase (CrtM) enzyme of methicillin resistant Staphylococcus aureus compared to the current inhibitor. Hence, this suggests that tetrangomycin has a potential to be used as an anti-methicillin resistant Staphylococcus aureus agent. Tetrangomycin also showed moderate free radical scavenging activity with 1,1-diphenyl-2-picryl-hydrazil. Tetrangomycin apparently decreased all of the studied cytokine (pro-inflammatory: interleukin 1B, interleukin 2, tumor necrosis factor and interleukin L6 and anti-inflammatory: interleukin 10) expression levels at IC50 concentrations in A459 (adenocarcinomic human alveolar basal epithelial) and LNCAP (human prostate adenocarcinoma) cell lines. In addition, it reduced Caspase 8 and 3 mRNA levels in LNCAP and A549 cells. This study describes for the first time novel in vitro immunosuppressive function of tetrangomycin by reducing the transcription of cytokine genes.

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Acknowledgments

This study was supported by the Scientific and Technical Research Council of Turkey (TBAG 109T843) and Dicle University Research Foundation (DUBAP-09-FF-45) as well as the United States National Science Foundation (DEB-1136662). The authors would like to thank the staff of the Princeton University NMR and Mass Spectrometry facilities for experimental support.

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, University of Dicle, Diyarbakir, 21280, Turkey

    Süleyman Özakin & Ebru İnce

  2. Department of Chemistry, Villanova University, Villanova, PA, 19085, USA

    Robert W. Davis, Thomas P. Umile & Kevin P. C. Minbiole

  3. Division of Natural and Computational Sciences, Gwynedd Mercy University, Gwynedd Valley, PA, 19437, USA

    Thomas P. Umile

  4. Department of Chemistry, Faculty of Science, University of Dicle, Diyarbakir, 21280, Turkey

    Necmettin Pirinccioglu & Murat Kizil

  5. Department of Biology, Faculty of Science and Art, Pamukkale University, Kinikli-Denizli, 20070, Turkey

    Gurbet Celik & Alaattin Sen

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  1. Süleyman Özakin
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  2. Robert W. Davis
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Correspondence to Ebru İnce.

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Özakin, S., Davis, R.W., Umile, T.P. et al. The isolation of tetrangomycin from terrestrial Streptomyces sp. CAH29: evaluation of antioxidant, anticancer, and anti-MRSA activity. Med Chem Res 25, 2872–2881 (2016). https://doi.org/10.1007/s00044-016-1708-6

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  • DOI: https://doi.org/10.1007/s00044-016-1708-6

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