• Bis-Picolinamide ruthenium (III) dihalide complexes: dichloride to diiodide exchange generates single trans isomers with high potency and cancer cell selectivity

      Basri, A.M.; Lord, Rianne M.; Allison, Simon J.; Rodríguez-Bárzano, A.; Lucas, S.J.; Janeway, F.X.; Shepherd, H.J.; Pask, C.M.; Phillips, Roger M.; McGowan, P.C. (2017-05-05)
      A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type RuX2L2 (X = Cl or I and L = picolinamide) have been synthesised and characterised. They exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies reveal a mixture of cis and trans isomers for the RuCl2L2 complexes but upon a halide exchange reaction to RuI2L2, only single trans isomers are present. High cytotoxic activity against human cancer cell lines was observed, with potencies for some complexes similar to or better than cisplatin. Conversion to RuI2L2 substantially increased activity towards cancer cell lines by >12-fold. The RuI2L2 complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with >4-fold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, indicating the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. Selected complexes were also tested against non-cancer ARPE-19 cells. The RuI2L2 complexes are more potent than the RuCl2L2 analogues, and also more selective towards cancer cells with a selectivity factor >7-fold.
    • Increasing anti-cancer activity with longer tether lengths of group 9 Cp* complexes

      Lucas, S.J.; Lord, Rianne M.; Basri, A.M.; Allison, Simon J.; Phillips, Roger M.; Blacker, A.J.; McGowan, P.C. (2016-04)
      Here in, we report the cytotoxicity of both rhodium and iridium functionalised Cp* analogues of the [Cp*MCl2]2 dimers. The functionalised dimers contain a hydroxy tethered arm of differing carbon length. These show promising IC50 values when tested against HT-29, A2780 and cisplatin-resistant A2780cis human cancer cell lines, with the cytotoxicity improving proportionally with an increase in carbon tether length of the Cp* ring. The most promising results are seen for the 14-carbon Cp* tethered rhodium (2d) and iridium (3b) complexes, which show up to a 24-fold increase in IC50 compared to the unfunctionalised [Cp*MCl2]2 dimer. All complexes were potent inhibitors of purified thioredoxin reductase suggesting that disruption of cellular anti-oxidant function is one potential mechanism of action.
    • Synthesis of iridium and ruthenium complexes with (N,N), (N,O) and (O,O) coordinating bidentate ligands as potential anti-cancer agents

      Lucas, S.J.; Lord, Rianne M.; Wilson, R.L.; Phillips, Roger M.; Sridharan, V.; McGowan, P.C. (2012-12-07)
      Several Ru-arene and Ir–Cp* complexes have been prepared incorporating (N,N), (N,O) and (O,O) coordinating bidentate ligands and have been found to be active against both HT-29 and MCF-7 cell lines. By incorporating a biologically active ligand into a metal complex the anti-cancer activity is increased.