Per the American Cancer Society’s Cancer Facts and Figures there were an estimated 1.6 million new cases of cancer in 2016. Many treatments are currently available however they exhibit serious side effects due to poor selectivity. Efforts to create safer anticancer therapies and limit undesired side effects include the development of site-directed treatments. We have developed a series of ruthenium complexes of the type [Ru(N,N’)2(6,6’-dihydroxybipyridine)]2+ as potential anticancer prodrugs that are cytotoxic when exposed to light but maintain low toxicity in the dark. The rate of photodissociation is increased in acidic conditions but the complexes are relatively stable at neutral pH values. Since cancer cells are known to have a lower extracellular pH due to increased metabolism, we hypothesize that our complexes exhibit selective cytotoxicity when in the presence of cancer cells and can be activated by photodynamic therapy (PDT). Initial results were reported recently [Inorg. Chem. 2017, 56, 7519] and in this talk we will describe the results of further recent studies. Our studies indicate that rate of cellular uptake has an impact on toxicity. This is being investigated by determining the distribution coefficient in an octanol/water system as a function of pH as a potential model for passive diffusion. New complexes that vary the overall charge of the ruthenium complex are currently being synthesized and studied to determine their effects on uptake and toxicity.

Development and study of novel ruthenium complexes as potential dual-activated anticancer prodrugs: The role of pH in uptake and the use of cytotoxic ligands

255th National Meeting (2018)

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