The potent oxidant anticancer activity of organoiridium catalysts.
Bottom Line: The pyridine ligand protects 1-py from rapid reaction with intracellular glutathione.The unprecedented ability of these iridium complexes to generate H2 O2 by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated.Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.
Affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK).Show MeSH
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Mentions: Complex 1-py showed high potency with an IC50 value (the concentration at which 50 % of cell growth is inhibited) of 120 nm towards A2780 human ovarian cancer cells, which renders it six times more active than 1-Cl,6c and approximately ten times more active than cisplatin (Figure 2 a and Table S3). Moreover, 1-py is thirteen times less toxic towards normal cells (MRC-5 human lung fibroblast cells) than towards A2780 cancer cells, whereas 1-Cl has a much lower selectivity factor of four (Figure 2 a). Interestingly, the antiproliferative activity of 1-py towards A2780 cells after exposure for four hours is the same as that after 24 hours, which implies that the onset of cell death is a relatively rapid process (Figure S2 and Table S4).
Affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK).