Planta Med 2013; 79 - SL71
DOI: 10.1055/s-0033-1351896

Anti-cancer thymoquinone from Nigella sativa

WW Li 1, JO Rosa 1, MR Siddique 1, B Bajana 1, J Sulé-Suso 2, A Richardson 1
  • 1Guy Hilton Research Centre, Institute for Science and Technology in Medicine, Keele University, Stoke-On-Trent, ST4 7QB, UK
  • 2Cancer Centre, University Hospital of North Staffordshire, Stoke-on-Trent, ST4 6QG, UK

Quinones and phenolic compounds are important bioactive natural products in medicinal and dietary plants [1 – 3]. For example, thymoquinone (2-isopropyl-6-methyl-1,4-benzoquinone, TQ) is the main bioactive compound from Nigella sativa (black cumin) (Figure), showing various biological activities including anti-cancer activities [4]. Although much effort has been made to understand the mechanism of action of TQ, it is still elusive. TQ is not a fully substituted quinone which should be reactive towards thiol groups of proteins [5 – 7]. Here, we report the synthesis of deuterated TQ as a molecular probe for the protein targets in ovarian cancer cells and leukaemia cells and a stable internal standard for the accurate quantification of TQ (stable isotope dilution method) in plant materials using mass spectrometry. In addition, TQ has been shown to bind to cysteines of haemoglobin and glutathione by HPLC and LC-ESI-MS, which indicates a possible covalent modification of protein targets in cancer cells. A MS-based metabolic approach has also been used to understand the change of metabolites in K562 leukaemia cells after addition of TQ. The significant decrease of many intermediates of TCA cycle and lipids has been observed. Moreover, a number of thioether and amino TQ analogues are prepared for the study of structure-activity relationships, in particular, to prove if the thiol addition reaction is responsible for the biological activity of TQ and search for more potent analogues.

Fig. 1


[1] Link A, Balaguer F, Goel A. (2010) BIOCHEM. PHARMACOL., 80, 1771 – 1792.

[2] Li WW, Barz W. (2005) TETRAHEDRON LETT., 46, 2973 – 2977.

[3] Li WW, Barz W. (2006) PLANTA MED., 72, 248 – 254.

[4] Woo C C, Kumar AP, Sethi G, Tan KH. (2012) BIOCHEM. PHARMACOL., 83, 443 – 451.

[5] Li WW, Heinze J, Haehnel W. (2005) J. AM. CHEM. SOC., 127, 6140 – 6141.

[6] Li WW, Hellwig P, Ritter M, Haehnel W. (2006) CHEM. EUR. J., 12, 7236 – 7245.

[7] Lu S, Li WW, Rotem D, Mikhailova E, Bayley H. (2010) NATURE CHEM., 2, 821 – 828.