title: Anti-MRSA-acting carbamidocyclophanes H-L from the Vietnamese cyanobacterium Nostoc sp. CAVN2.
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.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Preisitsch
authors.affiliation: Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbrücken, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Harmrolfs
authors.affiliation: 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.
authors.forename: Hang T L
authors.initials: HT
authors.lastname: Pham
authors.affiliation: Department of Pharmaceutical Biotechnology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: Stefan E
authors.initials: SE
authors.lastname: Heiden
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Füssel
authors.affiliation: Sealife PHARMA GmbH, Tulln, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wiesner
authors.affiliation: Sealife PHARMA GmbH, Tulln, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Pretsch
authors.affiliation: Cyano Biotech GmbH, Berlin, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Swiatecka-Hagenbruch
authors.affiliation: 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.
authors.forename: Timo H J
authors.initials: TH
authors.lastname: Niedermeyer
authors.affiliation: Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, Saarbrücken, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mundt
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D046937:Nostoc / Q000145:classification / Q000378:metabolism*; D010802:Phylogeny
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic