Planta Med 2009; 75 - SL5
DOI: 10.1055/s-0029-1234260

Differential cytotoxic and prooxidnant activity of knipholone and knipholone anthrone

S Habtemariam 1, E Dagne 2
  • 1Pharmacognosy Research Laboratories, Medway School of Science, University of Greenwich, Chatham-Maritime, Kent ME4 4TB, UK
  • 2African Laboratory for Natural Products, Department of Chemistry, Addis Ababa University, PO Box 30270, Addis Ababa, Ethiopia

Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological effects including in vitro antioxidant [1] and antimicrobial properties [2]. The present study was designed to investigate the comparative in vitro cytotoxic activity and the possible mechanism of action of these two compounds. We demonstrated that KA is by order of magnitude more cytotoxic to mammalian cells than KP. In parallel with the demonstrated cytotoxic effect, KA but not KP induces prooxidative DNA damage in the presence of copper ions. In order to establish the possible involvement of reactive oxygen species in the KA-mediated prooxidative effect, we investigated the protective effect of several metal chelators and reactive oxygen species scavengers. Our data suggest that reactive oxygen species such as hydrogen peroxide are involved and a good correlation between prooxidative action, antioxidant effect and cytotoxicity is established for these two structural analogues. The chemistry, pharmacology and potential medicinal/toxicological potential of these compounds are discussed.

Acknowledgements: This research was supported by the HEFCE capability funding.

References: [1] Habtemariam, S. (2007)J. Food Chem. 102:1042–1047.

[2] Bringmann, G. et al. (2008) Nat. Prod. Rep. 25:696–718.