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Sugar-linked Ruthenium-anticancer Complexes

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New drug design challenges tumour resistance

Second only to heart disease as cause of death, the number of cancer deaths in Europe is expected to surpass 2 million annually by 2020. New anti-cancer drugs are needed to stave off this drastic socioeconomic problem.

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Early diagnosis and improved treatment options have significantly boosted the fight against cancer in recent years. However, many obstacles remain as various major tumours effectively resist treatment. The 'Sugar-linked ruthenium-anticancer complexes' (Suruco) project team undertook a novel approach to overcoming this problem by turning their attention to a novel drug design strategy. The particular drug candidates are new ruthenium(II)- and osmium(II)-arene complexes based on the sugar phosphite moiety. A moiety is one part of a molecule that may include functional groups as substructures (also known as scaffolds). In recent years, these complexes have shown promise as anti-cancer drug candidates: the metal-arene (RuII) motif is well suited to rational drug design. This scaffold also provides the means for fine-tuning certain desirable drug properties such as solubility and stability. To take advantage of the fact that cancer cells usually have increased glucose uptake under conditions of oxygen starvation (i.e. hypoxia), the Suruco team studied how a carbohydrate moiety influenced the accumulation and uptake of specifically prepared Ru(II)- and osmium(II)-arene compounds. The intricate experiment revealed enhanced cellular uptake, suggesting that the newly created sugar-derived ligands can indeed increase accumulation of the drug in cancer cells. Another positive study result was that the metal cluster compounds showed excellent cytotoxicity on the human A2780, A2780cisR ovarian carcinoma cell lines. On completion of the project, researchers had achieved all research objectives and project results offer a new basis on which to conduct further related studies.

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