Platinum-based drugs, such as cisplatin, carboplatin, and oxaliplatin, kill cancer cells by binding DNA. Although DNA-damaging agents have proven effective in the clinic, they suffer from serious drawbacks such as cross-resistance and toxicity to healthy cells. To overcome these hurdles, our lab has been investigating the anticancer potential of rhenium complexes. We have recently discovered that rhenium isonitrile complexes kill cancer cells by inducing endoplasmic reticulum (ER) stress, which leades to apoptosis. These highly potent rhenium complexes are not cross-resistant with platinum-based drugs, and they are well-tolerated by mice. To better understand the complexes' molecular mechanism of action and develop more powerful agents, we have synthesized a library of rhenium isonitrile complexes and related their structure to their anticancer activity. We have also evaluated the efficacy of the lead compound in ovarian cancer tumor xenografts. These results establish rhenium isonitrile complexes as promising drug candidates with high potency and a novel mechanism of action.

Investigation of rhenium tricarbonyl isonitrile complexes as alternatives to platinum anticancer agents

2019 Fall National Meeting

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