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

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.