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J Antibiot (Tokyo). 2015 Mar;68(3):165-77. doi: 10.1038/ja.2014.118. Epub 2014 Sep 3.

Anti-MRSA-acting carbamidocyclophanes H-L from the Vietnamese cyanobacterium Nostoc sp. CAVN2.

Author information

1
Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany.
2
Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbrücken, Germany.
3
1] Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany [2] Department of Plant Physiology and Biochemistry, Faculty of Biology, University of Science, Hanoi, Vietnam.
4
Department of Pharmaceutical Biotechnology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany.
5
Sealife PHARMA GmbH, Tulln, Austria.
6
Cyano Biotech GmbH, Berlin, Germany.
7
1] Cyano Biotech GmbH, Berlin, Germany [2] Interfaculty Institute of Microbiology and Infection Medicine, Eberhard Karls University, Tübingen, Germany [3] German Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.

Abstract

The methanol extract of the Vietnamese freshwater cyanobacterium Nostoc sp. CAVN2 exhibited cytotoxic effects against MCF-7 and 5637 cancer cell lines as well as against nontumorigenic FL and HaCaT cells and was active against methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. High-resolution mass spectrometric analysis indicated the presence of over 60 putative cyclophane-like compounds in an antimicrobially active methanol extract fraction. A paracyclophanes-focusing extraction and separation methodology led to the isolation of 5 new carbamidocyclophanes (1-5) and 11 known paracyclophanes (6-16). The structures and their stereochemical configurations were elucidated by a combination of spectrometric and spectroscopic methods including HRMS, 1D and 2D NMR analyses and detailed comparative CD analysis. The newly described monocarbamoylated [7.7]paracyclophanes (1, 2, 4 and 5) differ by a varying degree of chlorination in the side chains. Carbamidocyclophane J (3) is the very first reported carbamidocyclophane bearing a single halogenation in both butyl residues. Based on previous studies a detailed phylogenetic examination of cyclophane-producing cyanobacteria was carried out. The biological evaluation of 1-16 against various clinical pathogens highlighted a remarkable antimicrobial activity against MRSA with MICs of 0.1-1.0 μM, and indicated that the level of antibacterial activity is related to the presence of carbamoyl moieties.

PMID:
25182484
DOI:
10.1038/ja.2014.118
[Indexed for MEDLINE]

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