Four new diterpenoids from the roots of Euphorbia fischeriana Hong-Bing Wang a, ⁎, Wei Chen a , Ying-Ying Zhang a , Xiao-Yang Wang a,b , Li-Ping Liu a , Ling-Jiang Tong c , Yi Chen c a School of Life Sciences & Technology, Tongji University, Shanghai 200092, PR China b School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, PR China c Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China article info abstract Article history: Received 24 April 2013 Accepted in revised form 5 September 2013 Available online 13 September 2013 Four new diterpenoids (1,4,5,9), together with 7 known diterpenoids (2,3,6–8,10,11), were isolated from the roots to Euphorbia fischeriana. On the basis of 1D and 2D NMR, HR-ESI-MS spectroscopic analysis, structures of the new compounds were elucidated as 11β-hydroxy- 8,14-epoxy-ent-abieta-13(15)-en-16,12-olide (1), 3,20-dihydroxy-ent-1(10), 15-rosadiene (4), 3,7- dihydroxy-ent-1(10), 15-rosadiene (5), ingenol 6,7-epoxy-3- tetradecanoate (9). The compounds isolated were evaluated for their cytotoxicity against four cancer cell lines (A549, BEL7402, HCT116, and MDA-MB-231). Three ingenol diterpenoids (9–11) showed significant cytotoxicity against A549 with IC 50 value of 3.35, 2.85, 2.88 μg/mL, respectively. © 2013 Elsevier B.V. All rights reserved. Keywords: Euphorbia fischeriana Diterpenoids Cytotoxicity 1. Introduction The genus Euphorbia is the largest in the family Euphorbia- ceae, comprising more than 2000 species [1]. Some species of the genus Euphorbia have been used as folk medicine for the treatment of skin diseases, gonorrhea, migraine, and intes- tinal parasites and as wart cures [2]. Among them, Euphorbia fischeriana Steud is a perennial herbaceous plant with milky juice, distributed mainly in north China. The dried roots, named “lang-du” in traditional Chinese medicine, have been used as a remedy for the treatment of cancer, ascites, and edema [3]. The chemical constituents of the roots have been investigated and a variety of diterpenoids have been reported [4–10]. 17- Hydroxy-jolkinolide B, a abietane diterpenoids from the roots of Euphorbia fischeriana, can inhibit STAT3 signaling by covalently cross-linking JAK family kinases and induce apopto- sis of human cancer cells [11]. It is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. These results encouraged us to reinvestigate the roots of Euphorbia fischeriana for additional new bioactive compounds, which has led to the isolation of four new diterpenoids (1, 4, 5, 9) and seven known diterpenoids (2, 3, 6–8, 10, 11)(Fig. 1). In this paper, we describe isolation, structural elucidation, and cytotoxic activity of the isolated compounds. 2. Experimental 2.1. General Optical rotations were measured on a Perkin Elmer 341 polarimeter. UV spectra were obtained on a Shimadzu UV-2500 spectrophotometer. IR spectra were recorded on a Nicolet Magna IR spectrophotometer. The NMR spectra were run on a Bruker AM-400 spectrometer with TMS as internal standard. HR-ESI-MS spectra were carried out on a Bruker Apex IV FT-MS spectrometer. Column chromatographic separations were carried out on silica gel H-60 (Qingdao Haiyang Chemical Group Corporation, Qingdao, People's Republic of China), Sephadex LH-20 (Pharmacia Biotech AB, Uppsala, Sweden), and LiChroprep RP-18 (40–63 μm, Merck). TLC was carried out on Silica gel HSGF254 plates (Yantai Chemical Industrial Institute, Yantai, People's Republic of Fitoterapia 91 (2013) 211–216 ⁎ Corresponding author. Tel./fax: +86 21 65983693. E-mail address: hbwang@tongji.edu.cn (H.-B. Wang). 0367-326X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.fitote.2013.09.003 Contents lists available at ScienceDirect Fitoterapia journal homepage: www.elsevier.com/locate/fitote