NF- κ B-Inhibiting Naphthopyrones from the Fijian Echinoderm Comanthus parvicirrus

1. NF-κB-Inhibiting Naphthopyrones from the Fijian Echinoderm Comanthus parvicirrus Florence Folmer,† William T. A. Harrison,† Jioji N. Tabudravu,† Marcel Jaspars,*,† William Aalbersberg,‡ Klaus Feussner,‡Anthony D. Wright,§ Mario Dicato,⊥ and Marc Diederich⊥ Department of Chemistry, UniVersity of Aberdeen, Old Aberdeen, AB24 3UE, U.K., Institute of Applied Sciences, Faculty of Science and Technology, UniVersity of the South Pacific, P.O. Box 1168, SuVa, Fiji Islands, Australian Institute of Marine Science, TownsVille 4810, Queensland, Australia, and Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, Rue Edward Steichen, L-2540 Luxembourg, Luxembourg Received June 18, 2007 學 生：賴建豪 簡嵐翔授課老師：詹于誼 老師日 期：97.06.10

2. outline • 前言 • 動物形態介紹 • 抽取與分離 • 構造研究 • 細胞活性試驗 • 結論

3. Comanthus parvicirrus (小卷海齒花) 動物界 (Animalia) 棘皮動物門 (Echinodermata) 海百合綱 (Crinoidea) 關節亞鋼 (Articulata) 海羊齒目 (Comatulida) 櫛羽星科 (Comasteridae) 為一種始見於石炭紀的棘皮動物，生活於海裡， 具多條腕足，身體呈花狀，錶面有石灰質的殼。 常棲息於岩縫、石、軟珊瑚的基部。

4. Nuclear factor κB (NF-κB) is an inducible transcription factor that plays a key role in cancer development and inflammation. Karin, M. Nature 2006, 441, 431–436. • The majority of the compounds known to date as potent NF-κB inhibitors are plant-derived isoprenoids and polyphenolics. Aggarwal, B. B.; Shishodia, S. Biochem. Pharmacol. 2006, 71, 1397–1421. • In general, echinoderms belonging to the genus Comanthus exhibit a low structural diversity, consisting mainly of aromatic polyketides. Kent, R.; Smith, I. R.; Sutherland, M. D. Aust. J. Chem. 1970, 23, 2325–2335.

5. Only a few natural products, including quinones, anthraquinones, and naphthopyrones, have been isolated from representatives of the genus Comanthus so far. Sakuma, Y.; Tanaka, J. I.; Higa, T. Aust. J. Chem. 1987, 40, 1613–1616. • The extract of C. parvicirrus yielded only two major compounds, 6-methoxycomaparvin (1) and 6-methoxycomaparvin 5-methyl ether (2). • Both 1 and 2 were shown to inhibit TNF-R-induced NF-κB activation by ≧74% at a concentration of 100 μg/mL.

6. 抽取與分離

7. General Experimental Procedures. • UV spectra were measured in MeOH on a Perkin-Elmer Lambda 15 UV/vis spectrometer. • IR spectra were recorded on an ATI Mattson Genesis FTIR, using KBr discs. • 1H, 13C, and all other NMR 2D experiments were recorded in CDCl3, either on a Varian Unity INOVA 400 MHz spectrometer or on a Bruker Avance 600 MHz spectrometer with a cryoprobe. • TMS was used as an internal reference for the 1H NMR spectra, and the CDCl3 signal at 77.0 ppm was used as a reference for 13C NMR spectra. • ESIMS was carried out on a Perseptive Biosystem Mariner LC-MS. • HRESIMS analysis was carried out at the EPSRC National Mass Spectrometry Service Centre in Swansea (UK). • HPLC separations were carried out using a Phenomenex reversed-phase (C18, 10 × 250 mm, 5 μm) • HPLC column and an HP1100 HPLC system (Agilent Technologies) with a diode array detector (DAD).

8. 抽取與分離 MeOH extract of C. parvicirrus (1.1g dry weight) Partitioned by H2O-CH2Cl2 fractionation H2O-soluble CH2Cl2-soluble Hexanes/10%MeOH Partitione 50% MeOH-soluble Extracted with CH2Cl2 CH2Cl2-soluble Reversed-phase HPLC Compound 1 (61 mg) Compound 2 (34 mg)

9. naphthopyrones 6-methoxycomaparvin (1) 6-methoxycomaparvin 5-methyl ether (2)