Development of Anticancer Ruthenium (II) Arene Thiocarboxylate Complexes
Ruthenium based complexes, which often exhibit lower toxicity in-vivo, are of high interest and hence offer an attractive option to the existing Pt based anti-cancer drugs. NAMI-A and KP1019 are two Ru-based complexes currently undergoing clinical trials to treat various forms of cancer, further demonstrating the potential use of Ru-based compounds as anti-cancer agents. A more contemporary approach to Ru centered anti-cancer agents has exploited ‘piano-stool’ complexes, often containing a para-cymene motif which helps to stabilize the Ru (II) oxidation state.3 With this in mind we have developed a novel class of Ru (II) bifunctional organometallic drugs for which subtle structural changes induce marked changes in activities against a variety of cancer cell lines. In vitro assays conducted on the 12 novel complexes have revealed that small structural changes in the complex significantly impact their biological activity. Interestingly, one of the Ru complexes synthesised exhibits high selectivity for in vitro models of aggressive breast cancers compared to other cultured cancerous and non-cancerous cell lines. A number of other biological assays have revealed the high stability and selective cytotoxicity of this Ru complex, further suggesting the novel compounds may possess good in vivo pharmacokinetics with reduced side effects.
Dr Liam Stephens performed his undergraduate masters and PhD at the University of Bath, UK, under the supervision of Professor Steven Bull. During his time as an undergraduate student, he spent one year working in industry at AkzoNobel, where he was involved in the development of new polymers to prevent fouling on marine vessels. After returning to Bath and completing his masters, he undertook a PhD which largely focused on the development of a novel class of vinyl isocyanide compounds for the treatment of MRSA infections. Since completing his PhD in 2018, Liam has undertaken his first post-doctoral position at Monash University, Australia. Under the supervision of Professor Phil Andrews, Liam has specifically been working on the development of new metal based compounds for their use as antibiotics and anticancer agents.