Dermacoccus abyssi sp. nov., strains MT1.1 and MT1.2 are actinomycetes isolated from Mariana Trench sediment at a depth of 10 898 m. Fermentation using ISP2 and 410 media, respectively, lead to production of seven new oxidized and reduced phenazine-type pigments, dermacozines A-G (1-7), together with the known phenazine-1-carboxylic acid (8) and phenazine-1,6-dicarboxylic acid (9). Extensive use was made of 1D and 2D-NMR data, and high resolution MS to determine the structures of the compounds. To confirm the structure of the most complex pentacyclic analogue (5) we made use of electronic structure calculations to compare experimental and theoretical UV-Vis spectra, which confirmed a novel structural class of phenazine derivatives, the dermacozines. The absolute stereochemistry of dermacozine D (4) was determined as S by a combination of CD spectroscopy and electronic structure calculations. Dermacozines F (6) and G (7) exhibited moderate cytotoxic activity against leukaemia cell line K562 with IC50 values of 9 and 7 mu M, respectively, while the highest radical scavenger activity was observed for dermacozine C (3) with an IC50 value of 8.4 mu M.
The authors are grateful to EPSRC National Mass Spectrometric Centre, University of Wales, Swansea, for mass spectrometric analysis. We also thank Sharon M. Kelly, Institute of Biomedical and Life Sciences, University of Glasgow, for CD measurements. We thank the Kaiko operation team and the crew of M.S. Yokosuka for collecting sediment samples. WMAM thanks the Egyptian
Government for a Ph.D. scholarship. ATB thanks the Leverhulme Trust for an Emeritus Fellowship. MJ is the recipient of a BBSRC Research Development Fellowship. This work also was supported in part by the “Recherche Cancer et Sang” foundation, Telˆ evie and the “Recherches Scientifiques Luxembourg (RSL)” ˆ association. MS is supported by a Telˆ evie grant. The authors ˆ thank the “Action Lions Vaincre le Cancer” and “Een Haerz fir ¨ kriibskrank Kanner” asbl for additional support. BFM thanks the Portuguese Foundation for Science and Technology for financial support (PTDC/FIS/73578/2006). All theoretical calculations were performed using the RINH/BioSS Beowulf cluster which is funded by the Scottish Government Rural and Environment Research and Analysis Directorate at the University of Aberdeen Rowett Institute of Nutrition and Health, Scotland with the assistance of Dr Tony Travis.
- radical-scavenging activity
- marine natural-products
- approxmate coulomb potentials
- auxiliary basis-set
- Gaussin-basis sets
- phenazine-1,6-dicarboxylic acid
- phenazine-1-carboxylic acid
- secondary metabolites