Cytotoxic phorbol esters of Croton tiglium.

Chemical investigation of the seeds of Croton tiglium afforded eight new phorbol diesters (three phorbol diesters, 1-3, and five 4-deoxy-4α-phorbol diesters, 4-8), together with 11 known phorbol diesters (nine phorbol diesters, 9-17, and two 4-deoxy-4α-phorbol diesters, 18 and 19). The structures of compounds 1-8 were determined by spectroscopic data information and chemical degradation experiments. The cytotoxic activities of the phorbol diesters were evaluated against the SNU387 hepatic tumor cell line, and compound 3 exhibited the most potent activity (IC50 1.2 μM).

[1]  K. Becker,et al.  Phorbol Esters: Structure, Biological Activity, and Toxicity in Animals , 2007, International journal of toxicology.

[2]  L. Delang,et al.  Prostratin and 12-O-tetradecanoylphorbol 13-acetate are potent and selective inhibitors of Chikungunya virus replication. , 2012, Journal of natural products.

[3]  K. Chantrapromma,et al.  Antimycobacterial activity of phorbol esters from the fruits of Sapium indicum. , 2003, Journal of Natural Products.

[4]  G. Cordell,et al.  Plant anticancer agents. XXVI. Constituents of Peddiea fischeri. , 1983, Journal of natural products.

[5]  H. Hausen,et al.  Persisting oncogenic herpesvirus induced by the tumour promoter TPA , 1978, Nature.

[6]  A. Kinghorn,et al.  Phorbol diester constituents of croton oil: separation by two-dimensional TLC and rapid purification utilizing reversed-phase overpressure layer chromatography (RP-OPLC). , 1988, Planta medica.

[7]  T. Kawahata,et al.  Anti-HIV-1 phorbol esters from the seeds of Croton tiglium. , 2000, Phytochemistry.

[8]  E. Hecker,et al.  Inflammatory, tumor initiating and promoting activities of polycyclic aromatic hydrocarbons and diterpene esters in mouse skin as compared with their prostaglandin releasing potency in vitro. , 1978, Cancer letters.

[9]  D. Scudiero,et al.  Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines. , 1988, Cancer research.

[10]  M. Neeman,et al.  Carbon-13 nuclear magnetic resonance spectroscopy of phorbol , 1979 .

[11]  G. Negri,et al.  Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae) , 2007 .

[12]  E. Hecker.  Cocarcinogenesis and tumor promoters of the diterpene Ester type as possible carcinogenic risk factors , 2004, Journal of Cancer Research and Clinical Oncology.

[13]  N. Colburn,et al.  Phorbol diester and epidermal growth factor receptors in 12-O-tetradecanoylphorbol-13-acetate-resistant and -sensitive mouse epidermal cells. , 1982, Cancer research.

[14]  T. Kawahata,et al.  12-O-acetylphorbol-13-decanoate potently inhibits cytopathic effects of human immunodeficiency virus type 1 (HIV-1), without activation of protein kinase C. , 1999, Chemical & pharmaceutical bulletin.

[15]  H. Häring,et al.  Analysis of traditional Chinese anticancer drugs by capillary electrophoresis. , 1998, Journal of chromatography. A.

[16]  S. M. Kupchan,et al.  Jatrophone, a novel macrocyclic diterpenoid tumor inhibitor from Jatropha gossypiifolia , 1970 .

[17]  A. Kinghorn,et al.  Short-chain phorbol ester constituents of croton oil , 1984 .

[18]  G. Qin,et al.  Diterpenoids from the roots of Euphorbia fischeriana. , 2006, Journal of natural products.

[19]  B. L. Duuren,et al.  Tumour-enhancing Activity of the Active Principles of Croton tiglium L. , 1963, Nature.

[20]  R. Bauer,et al.  [Isolation and detection of phorbolesters in crotonoil with HPLC.]. , 1983, Planta medica.