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We have designed and synthesized a novel group of small molecules (Novo-6, Novo-7, Novo-8 and Novo-9) that are structural analogues of cantharidin (2,3-dimethyl-7-oxobicyclo[2.2.1]heptane-2,3 dicarboxylic acid anhydride), a natural toxin derived from blister beetles, which has been used for over 2000yrs in traditional Chinese medicine and as an anticancer agent since 1264.The nephrotoxicity of cantharidin precludes its clinical use; however, norcantharidin (demethylated cantharidin) does not display this toxicity.Our synthetic efforts have therefore focused on novel norcantharidin compounds for the treatment of cancer.While cantharidin and norcantharidin are potent inhibitors of protein phosphatase (PP) 1 and 2A, the Novo-analogues are not PP inhibitors, although we are investigating the possibility of intracellular activation resulting in PP inhibition.Most importantly, they do show unprecedented selectivity against the growth of colorectal cancer cell lines (GIs0 0.8μM) while having little to no effect on cell lines derived from other tumour sites, an observation confirmed by the National Cancer Institute USA in a panel of 60 cancer cell lines.Of greater importance, these agents have no effect on normal colorectal (GI50 380μM) and normal hacmatopoietic blood cells (GI5o>100μM).