Isolation and Structure Characterization of Cytotoxic Phorbol Esters from the Seeds of Croton tiglium

Abstract Nine new and eleven known phorbol esters were isolated from an acetone extract of the seeds of Croton tiglium. Their structures were determined by extensive analysis of spectroscopic data. Eleven of these compounds were evaluated for their inhibition activity on human tumor cell lines HL-60 and lung carcinoma A549. 12-O-Tiglylphorbol-13-acetate (11), 12-O-(2-methyl)-butyrylphorbol-13-aetate (12), and 12-O-tiglylphorbol-13-isobutyrate (13) exhibited strong inhibition activity against both HL-60 and A549 cell lines with IC50 values ≤ 0.02 and ≤ 0.1 µg/mL, respectively. Compound 18 showed strong inhibition activity against the HL-60 cell line with an IC50 value of 0.02 µg/mL.

[1]  Bin Zhou,et al.  Cytotoxic Tigliane-Type Diterpenoids from Croton tiglium. , 2016 .

[2]  P. Baran,et al.  Nineteen-Step Total Synthesis of (+)-Phorbol , 2016, Nature.

[3]  J. Neyts,et al.  LC-MS²-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity. , 2015, Fitoterapia.

[4]  Y. Liu,et al.  Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium. , 2015, Bioorganic & medicinal chemistry letters.

[5]  T. Kang,et al.  Tigliane diterpenoids from the Euphorbiaceae and Thymelaeaceae families. , 2015, Chemical reviews.

[6]  M. Melzig,et al.  Identification of new phorbol ester derivatives in extracts from Croton tiglium L. seeds by UHPLC-MS/MS and the approach of a quantification method after alkaline hydrolysis , 2014 .

[7]  Yang Zhang,et al.  Tigliane Diterpene Esters from the Leaves of Croton tiglium , 2014 .

[8]  Lun Wang,et al.  Cytotoxic phorbol esters of Croton tiglium. , 2013, Journal of natural products.

[9]  Wenyuan Gao,et al.  Antinociceptive and Smooth Muscle Relaxant Activity of Croton tiglium L Seed: An In-vitro and In-vivo Study , 2012, Iranian journal of pharmaceutical research : IJPR.

[10]  X. Wang,et al.  Effects of essential oil from Croton tiglium L. on intestinal transit in mice. , 2008, Journal of ethnopharmacology.

[11]  Pillai Nr.  Gastro intestinal effects of croton tiglium in experimental animals. , 1999 .

[12]  N. Pillai.  GASTRO INTESTINAL EFFECTS OF CROTON TIGLIUM IN EXPERIMENTAL ANIMALS , 1999, Ancient science of life.

[13]  L. Pieters,et al.  13C NMR spectroscopy of phorbol esters , 1987 .

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