Cytotoxic Sesquiterpene Lactones from Aerial Parts of Xanthium sibiricum

Abstract

Chemical investigation of the aerial parts of Xanthium sibiricum led to the isolation of four new xanthanolide-type sesquiterpene lactones, including two xanthanolide dimers, pungiolide D (1) and pungiolide E (2), and two xanthanolide monomers, 8-epi-xanthatin-1α,5α-epoxide (3) and 1β-hydroxyl-5α-chloro-8-epi-xanthatin (4), together with four known compounds, pungiolide A (5), 8-epi-xanthatin-1β,5β-epoxide (6), xanthatin (7), and 11α,13-dihydro-8-epi-xanthatin (8). The structures of these compounds were elucidated on the basis of spectroscopic data analysis. Pungiolide D (1) displayed an unusual structure featuring a 5/5/6-fused tricyclic system in the unit B. Compound 4 was shown to be a rare sesquiterpene lactone containing halogen, and its absolute configuration was determined by X-ray crystallographic analysis. The evaluation of the cytotoxic activities of the isolated new compounds against the SNU387 liver and A-549 lung human cancer cell lines showed that compound 4 possessed significant in vitro cytotoxicity with an IC₅₀ value of 5.1 µM against SNU387 liver cells.

Key words

Xanthium sibiricum - Compositae - sesquiterpene lactones - xanthanolides - cytotoxicity

• References

• 1 Chen YL. Xanthium L. Flora Reipublicae Popularis Sinicae, Vol. 75. Beijing: Science Press; 1979
• 2 Chinese Pharmacopoeia Committee. Pharmacopoeia of China, Part 1. Beijing: Chemical Industry Press; 2005: 111-112
• 3 Winters TE, Geissmen TA, Safir D. Sesquiterpene lactones of Xanthium species. Xanthanol and isoxanthanol, and correlation of xanthinin with ivalbin. J Org Chem 1969; 34: 153-155
• 4 Mahmoud AA. Xanthanolides and xanthane epoxide derivatives from Xanthium strumarium . Planta Med 1998; 64: 724-727
• 5 Bui VB, Liu ST, Zhu JJ, Xiong J, Zhao Y, Yang GX, Xia G. Sesquiterpene lactones from the aerial parts of Xanthium sibiricum and their cytotoxic effects on human cancer cell lines. Phytochem Lett 2012; 5: 685-689
• 6 Macleod JK, Moeller PD, Franke FP. Two toxic kaurene glycosides from the burrs of Xanthium pungens . J Nat Prod 1990; 53: 451-455
• 7 Ma YT, Huang MC, Hsu FL, Chang HF. Thiazinedione from Xanthium strumarium . Phytochemistry 1998; 48: 1083-1085
• 8 Qin LP, Han T, Li HL, Zhang QY, Zheng HC. A new thiazinedione from Xanthium strumarium . Fitoterapia 2006; 77: 245-246
• 9 Han T, Li HL, Zhang QY, Zheng HC, Qin LP. New thiazinediones and other components from Xanthium strumarium . Chem Nat Compd 2006; 42: 567-570
• 10 Dai YH, Cui Z, Li JL, Wang D. A new thiaziedione from the fruits of Xanthium sibiricum . J Asian Nat Prod Res 2008; 10: 303-305
• 11 Agata I, Goto S, Hatano T, Nishibe S, Okuda T. 1,3,5-Tri-O-caffeoylquinic acid from Xanthium strumarium . Phytochemistry 1993; 33: 508-509
• 12 Roussakis C, Chinou I, Vayas C, Harvala C, Verbist JF. Cytotoxic activity of xanthatin and the crude extracts of Xanthium strumarium . Planta Med 1994; 60: 473-474
• 13 Nour AMM, Khalid SA, Kaiser M, Brun R, Abdallah WE, Schmidt TJ. The antiprotozoal activity of sixteen Asteraceae species native to Sudan and bioactivity guided isolation of xanthanolides from Xanthium brasilicum . Planta Med 2009; 75: 1363-1368
• 14 Vasas A, Hohmann J. Xanthane sesquiterpenoids: structure, synthesis and biological activity. Nat Prod Rep 2011; 28: 824-842
• 15 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55-63
• 16 Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg 1938; 27: 493-497
• 17 Cumanda J, Marinoni G, Debernardi M, Vidari G, Finzi PV. New Sesquiterpenes from Xanthium catharticum . J Nat Prod 1991; 54: 460-465
• 18 Ahmed AA, Mahmoud AA, El-Gamal AA. A xanthanolide diol and a dimeric xanthanolide from Xanthium species. Planta Med 1999; 65: 470-472
• 19 Ahmed AA, Jakupovic J, Bohlmann F, Regaila HA, Ahmed AM. Sesquiterpene lactones from Xanthium pungens . Phytochemistry 1990; 29: 2211-2215
• 20 Omar AA, Elrashidy EM, Ghazy NA, Metwally AM, Ziesche J, Bohlmann F. Xanthanolides from Xanthium spinosum . Phytochemistry 1984; 23: 915-916
• 21 Bohlmann F, Singh P, Joshi KC, Singh CL. Xanthanolides from Xanthium indicum . Phytochemistry 1982; 21: 1441-1443
• 22 Deuel PG, Geissman TA. Xanthinin. II. The structures of xanthinin and xanthatin. J Am Chem Soc 1957; 79: 3778-3783