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Cancer fighting compounds with two metals have unique properties
Better Together? Cancer fighting compounds with two metals have unique properties
The motivation – There is an ongoing need for the development of new drug candidates that can combat cancer. One strategy is to combine two different compounds that have sub-optimal anti-cancer properties; when combined, such compounds can possess new and exciting properties. This strategy has been demonstrated for platinum-based FDA-approved drugs, but less so for the emerging class of ruthenium-based drugs that are of interest in the Walsby group.
The discovery – The first group of compounds were based on a common ruthenium (Ru) based anti-cancer compound called “RAPTA” – these are broadly classified as inorganic “piano stool complexes” because of their shape. The authors designed, synthesized, and attached a second group, the iron (Fe)-containing molecule ferrocene. Ferrocene was the subject matter of the 1973 Nobel Prize in Chemistry and has long been investigated for potential medicinal properties. In total, they produced a series of five new Ru-Fe bimetallic compounds and tested their ability to slow the growth of colon cancer cells. In comparison with the individual Ru- or Fe-containing groups alone, the bimetallic compounds displayed 12- to 50-fold better activity in inhibiting cancer cell growth.
Its significance – The changes made to the Ru and Fe compounds were relatively simple. Such a strategy enables more rapid investigations and potential improvements to the anticancer properties of metal-containing molecules. Instead of inventing an entirely new class of compounds, this approach employs pairs of well-known molecules with biological activity. The most significant finding here is that the properties of the iron (ferrocene) group have the biggest impact on anti-cancer activity. Those properties can be tuned by the identity of the bridge group or by the Ru group. This finding inspires new approaches to the design and investigation of ferrocene drugs. Importantly, such ferrocene groups include an inexpensive and abundant metal, opening a way forward to the development of less costly cancer treatments.
Read the paper – “Activation by Oxidation: Ferrocene-Functionalized Ru(II)-Arene Complexes with Anticancer, Antibacterial, and Antioxidant Properties ” by Mu, CH; Prosser, KE; Harrypersad, S; MacNeil, GA; Panchmatia, R; Thompson, JR; Sinha, S; Warren, JJ; Walsby, CJ. Inorganic Chemistry 57(24): 15247-15261 (2018). DOI: 10.1021/acs.inorgchem.8b02542.
Website article compiled by Jacqueline Watson with Theresa Kitos