Planta Med 2010; 76 - P399
DOI: 10.1055/s-0030-1264697

Protein kinase inhibiting anthraquinones and NF-κB inhibiting naphthopyrones from the Phillippine echinoderm Comanthus parvicirrus

S Ebada 1, Y Chovolou 1, W Wätjen 1, V Wray 2, R Edrada-Ebel 3, M Kubbutat 4, P Proksch 1
  • 1Heinrich-Heine University, Duesseldorf, Germany, Institut of Pharmaceutical Biology and Biotechnology, Universitaetsstrasse 1, 40225 Duesseldorf, Germany
  • 2Helmholtz Zentrum für Infektionsforschung, Inhoffenstrasse 7, 38124 Braunschweig, Germany
  • 3University of Strathclyde, United Kingdom, Strathclyde Institute of Pharmacy and Biomedical Science, The John Arbuthnott Building, 27 Taylor Street, Glasgow G4 0NR Glasgow, United Kingdom
  • 4ProQinase GmbH, Freiburg, Germany, Breisacher Strasse 117, 79106 Freiburg, Germany

A bioassay-guided investigation of a Philippine specimen of the echinoderm Comanthus parvicirrus yielded ten compounds evenly divided into anthraquinones and naphthopyrones. Four of the five anthraquinones were identified as 1′-deoxyrhodoptilometrin (2) and rhodoptilometrin (3) along with their respective 6-O-sulfate derivatives (4 and 5) in addition to a new natural anthraquinone congener (1). The isolated naphthpyrones were comaparvin (6), 6-methoxycomaparvin (7), 6-hydroxycomaparvin-8-O-sulfate (10), 6-methoxycomaparvin-5-methylether (8), and its 8-O-sulfate derivative (9). The structures of the isolated compounds were unambiguously assigned on the basis of spectroscopic methods. The absolute configuration of 3 and 5 was determined as (S)-(–) isomer. The isolated compounds were evaluated for their antibacterial, antifungal, antiviral and cytotoxic activities. In the cytotoxicity (MTT) assay against mouse lymphoma L5178Y cells, 2 and the unseparable mixture of 6 and 7 exhibited pronounced activity (IC50 values of 7.71 and 16.5 µM, respectively) compared to kahalalide F (IC50=4.3 µM) which was tested and proven to be mainly through induction of apoptosis. Moreover amongst the tested compounds for the protein kinase inhibitory activity against 24 different enzymes, anthraquinone congeners (2-5) and the unseparable naphthopyrone mixture (6/7) exhibited the most potent and selective behaviour with IC50 values between 1.8 and 33 µM. Compounds (1-3) and (6-8) were also tested for their potential to inhibit the activation of the transcription factor NF-κB, which plays an important role in cancer development and inflammation. Only naphthopyrones (6-8) significantly inhibited NF-κB activity (IC50's of 50–100 µM) and their mechanism of action was investigated.