Chemical and biological investigations of new vanadium compounds: determining their potential in the treatment of cancer

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Globally, the treatment of cancer is a substantial economic burden and the effects of cancer have a detrimental impact on the lives of patients and their families, potentially leading to further physical and mental illnesses. The current clinically used metal-based compounds (e.g. cisplatin, oxaliplatin and carboplatin) work by targeting DNA, however, they do not distinguish between cancerous and normal cells. They lead to adverse side effects, including renal failure, neurotoxicity and nausea. Many of the tumours become resistant to these platinum drugs, therefore, there is an urgent need for new drugs which selectively target and eradicate the cancerous cells, whilst minimising the associated side effects.The PI's recently published work highlighted new vanadium drugs which are more active than the clinically used platinum drugs and more selective for cancerous cells. Importantly, the ligands can be modified to incorporate a wide range of functionalities and allow us to determine structure-activity relationships. Also, the complexation of these ligands with vanadium will use our own literature methods, which will allow effective and efficient establishment of compound libraries. The proposed research will also investigate the drugs' distribution and accumulation within cells, and provide insights to the cellular targets and modes of actions. Furthermore, the drugs' activities will be measured in 3D cell culture models, as their environment is closer in nature to real-life tumours. This will enable the PI to identify more suitable and selective drugs, which can be taken towards clinical trials. Overall, this cheap and straight-forward drug design, coupled with in depth "tumour-like" studies, will provide new alternatives to cost-effective and targeted treatment.