Book Chapter Details
Mandatory Fields
E.C. O’ Sullivan, C.M. Miller, F.M. Deane, F.O. McCarthy
2012 November
Studies in Natural Products Chemistry
Emerging targets in the bioactivity of Ellipticines and derivatives
Elsevier Science Publishers
Amsterdam, Netherlands
In Press
Optional Fields
ellipticine, ellipticinium salts, cancer, DNA, topoisomerase, kinase, p53, mitochondria, bio-oxidation
Ellipticine was first isolated from the leaves of the tropical evergreen tree, Oschrosia Elliptica Labill (family Apocynaceae) by Goodwin et al. in 1959. It has been the focus of extensive chemical and pharmacological research since the discovery of its antitumour effects. Biologically, ellipticine presents a challenging and interesting focus of research. Early mechanisms of action focused on the intercalative and topoisomerase inhibitory properties of ellipticine. This was followed by elucidation of its bio-oxidation and formation of cytotoxic adducts with DNA. Previous extensive biological reviews of ellipticine by Auclair (1987) and Garbett  & Graves (2004) have focused mainly on these modes of action. More recently, and particularly in the last decade, increasing evidence has come to light regarding the cell cycle effects of ellipticine. To date, it has been demonstrated that ellipticine is capable of interacting with p53 tumour suppressor protein, Akt kinase and c-Kit kinase whilst effects on other cellular proteins are still being elucidated. Clearly ellipticine exhibits a multimodal cytotoxic activity, however it has yet to be determined which one of these actions is primarily responsible for its anti-cancer effects.
Derivatives of ellipticine such as 9-hydroxy-2-methylellipticinium acetate (NHME) and 2-(diethylaminoethyl)-9-hydroxyellipticinium chloride have progressed to clinical trials. While possessing attractive side effects profiles, neither has made a significant clinical impact with roles in salvage rather than frontline therapy. Therefore the challenge to produce more potent and targeted analogues of ellipticine remains. Recent developments which have further elucidated its biological effects may facilitate this process
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