Fatty acid synthase inhibitory activity of acylphloroglucinols isolated from Dryopteris crassirhizoma.

Fatty acid synthase (FAS) is emerging as a potential therapeutic target to treat cancer and obesity. Bioassay-guided fractionation of a MeOH extract of the rhizomes of Dryopteris crassirhizoma (Dryopteridaceae), using an in vitro FAS inhibitory assay, resulted in the isolation of a series of acylphloroglucinols, as the active principles. The isolates 1-10 inhibited FAS with IC50 values ranging from 23.1+/-1.4 to 71.7+/-3.9 microM. The results of the present study indicate that the acylphloroglucinol derivatives could be considered to be a promising class of FAS inhibitors.

[1]  Bing-hui Li,et al.  Inhibitory effects of flavonoids on animal fatty acid synthase. , 2004, Journal of biochemistry.

[2]  Mauri Lounasmaa Dérivés Phloroglucinoliques des Fougères du Genre Dryopteris , 1978 .

[3]  N. Nakamura,et al.  Kaempferol acetylrhamnosides from the rhizome of Dryopteris crassirhizoma and their inhibitory effects on three different activities of human immunodeficiency virus-1 reverse transcriptase. , 2001, Chemical & pharmaceutical bulletin.

[4]  M. Lane,et al.  Monitoring energy balance: metabolites of fatty acid synthesis as hypothalamic sensors. , 2005, Annual review of biochemistry.

[5]  G. Cordell,et al.  Constituents of the leaves and twigs of Calyptranthes pallens collected from an experimental plot in Southern Florida. , 2005, Journal of natural products.

[6]  S. Wakil,et al.  [7a] Fatty acid synthase from chicken liver , 1975 .

[7]  C. Townsend,et al.  Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts. , 2000, Cancer research.

[8]  S. Nishibe,et al.  A phloroglucinol derivative of Dryopteris abbreviata , 1982 .

[9]  C. Townsend,et al.  Synthesis and antitumor activity of an inhibitor of fatty acid synthase , 2000 .

[10]  J. Swinnen,et al.  Induction of Cancer Cell Apoptosis by Flavonoids Is Associated with Their Ability to Inhibit Fatty Acid Synthase Activity* , 2005, Journal of Biological Chemistry.

[11]  C. Townsend,et al.  Application of a flexible synthesis of (5R)-thiolactomycin to develop new inhibitors of type I fatty acid synthase. , 2005, Journal of medicinal chemistry.

[12]  J. Swinnen,et al.  RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells. , 2003, Cancer research.

[13]  Ren-bo An,et al.  Antioxidant activity of two phloroglucinol derivatives from Dryopteris crassirhizoma. , 2003, Biological & pharmaceutical bulletin.

[14]  F. Kuhajda Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. , 2000, Nutrition.

[15]  T. Yoshida,et al.  Ichthyotoxic phloroglucinol derivatives from Dryopteris fragrans and their anti-tumor promoting activity. , 2000, Chemical & pharmaceutical bulletin.

[16]  C. Widén,et al.  Phloroglucinol derivatives from Dryopteris fusco-atra and D. hawaiiensis , 1991 .

[17]  S. Wakil,et al.  Fatty acid synthesis and its regulation. , 1983, Annual review of biochemistry.

[18]  J. F. Stevens,et al.  Acylphloroglucinols and flavonoid aglycones produced by external glands on the leaves of two dryopteris ferns and currania robertiana , 1998 .

[19]  L. Jacobs,et al.  Fatty acid synthesis: a potential selective target for antineoplastic therapy. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  K. Bae The Medicinal Plants of Korea , 2000 .

[21]  H. Nishino,et al.  Anti-tumor promoting activity of Dryopteris phlorophenone derivatives. , 1996, Cancer letters.

[22]  M. Arisawa,et al.  Cytotoxic and antitumor constituents in pericarps of Mallotus japonicus. , 1990, Planta medica.

[23]  C. Townsend,et al.  Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. , 2000, Science.

[24]  M. C. Archer,et al.  Fatty acid synthase is a potential molecular target for the chemoprevention of breast cancer. , 2004, Carcinogenesis.