@article{63018632431b4bccae9b4ea281f3b720,
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.",
keywords = "antiinfective agent, carbamidocyclophane H, carbamidocyclophane I, carbamidocyclophane J, carbamidocyclophane K, carbamidocyclophane L, cyclophane, fusidic acid, methanol, mitoxantrone, paracyclophane derivative, unclassified drug, vancomycin, antineoplastic antibiotic, antibacterial activity, antimicrobial activity, Article, bacterial strain, biological activity, carbamoylation, chlorination, circular dichroism, controlled study, cyanobacterium, drug cytotoxicity, drug isolation, drug structure, electrospray mass spectrometry, freshwater species, halogenation, high performance liquid chromatography, human, human cell, keratinocyte, mass spectrometry, MCF 7 cell line, methicillin resistant Staphylococcus aureus, minimum inhibitory concentration, nonhuman, Nostoc, nucleotide sequence, phylogeny, priority journal, proton nuclear magnetic resonance, stereochemistry, Streptococcus pneumoniae, time of flight mass spectrometry, Viet Nam, classification, drug effects, metabolism, microbial sensitivity test, nuclear magnetic resonance spectroscopy, tumor cell line, Cyanobacteria, Nostoc sp., Anti-Bacterial Agents, Antibiotics, Antineoplastic, Cell Line, Tumor, Circular Dichroism, Humans, Magnetic Resonance Spectroscopy, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Phylogeny",
author = "M. Preisitsch and K. Harmrolfs and H.T. Pham and S.E. Heiden and A. F{\"u}ssel and C. Wiesner and A. Pretsch and M. Swiatecka-Hagenbruch and T.H.J. Niedermeyer and R. M{\"u}ller and S. Mundt",
note = "Funding Information: Michael Preisitsch was financially supported in part by a grant of Landesgraduiertenf{\"o}rderung MV, Ernst-Moritz-Arndt-University, Greifswald. The Vietnam National Foundation for Science and Technology Development is thanked for supporting the work of Dr Hang TL Pham. We thank Professor Philip Williams (Department of Chemistry, University of Hawaii, Honolulu, USA) and Professor Yoshiharu Iwabuchi (Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan) for providing (-)-cylindrocyclo-phane A and the synthetic analog. General support from Cyano Biotech GmbH, Berlin, Germany, is acknowledged. We are also grateful to Mrs Jana Kumpfm{\"u}ller (Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany) for her assistance with the molecular biological investigations as well as Mrs Monika Beerbaum (Leibniz-Institute of Molecular Pharmacology (FMP), Berlin, Germany) for recording 1H-NMR spectra of the known compounds, Professor Klaus Weisz (Institute of Biochemistry, Ernst-Moritz-Arndt-University, Greifswald, Germany) for kindly providing the CD spectrometer and Dr Olaf Morgenstern and Janine Technau (Institute of Pharmacy, Ernst-Moritz-Arndt-University, Greifswald, Germany) for measuring the IR spectra. Publisher Copyright: {\textcopyright} 2015 Japan Antibiotics Research Association.",
year = "2014",
month = sep,
day = "3",
doi = "10.1038/ja.2014.118",
language = "English",
volume = "68",
pages = "165--177",
journal = "Journal of Antibiotics",
issn = "0021-8820",
publisher = "Springer Nature",
number = "3",
}