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The potent oxidant anticancer activity of organoiridium catalysts.

Liu Z, Romero-Canelón I, Qamar B, Hearn JM, Habtemariam A, Barry NP, Pizarro AM, Clarkson GJ, Sadler PJ - Angew. Chem. Int. Ed. Engl. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK).

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Related in: MedlinePlus

Antiproliferative activity. a) IC50 in A2780 cancer cells and MRC-5 normal lung fibroblasts of 1-py, 1-Cl,6c and CDDP. b) GI50, TGI, and LC50 values (μm) of 1-Cl,7 1-py, and CDDP in the NCI-60 screen. c) Heat map for GI50 values of 1-Cl, 1-py, CDDP, and oxaliplatin (OXA). The deep red color corresponds to the highest activity, whereas the deep blue color represents the lowest activity.
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fig02: Antiproliferative activity. a) IC50 in A2780 cancer cells and MRC-5 normal lung fibroblasts of 1-py, 1-Cl,6c and CDDP. b) GI50, TGI, and LC50 values (μm) of 1-Cl,7 1-py, and CDDP in the NCI-60 screen. c) Heat map for GI50 values of 1-Cl, 1-py, CDDP, and oxaliplatin (OXA). The deep red color corresponds to the highest activity, whereas the deep blue color represents the lowest activity.

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).


The potent oxidant anticancer activity of organoiridium catalysts.

Liu Z, Romero-Canelón I, Qamar B, Hearn JM, Habtemariam A, Barry NP, Pizarro AM, Clarkson GJ, Sadler PJ - Angew. Chem. Int. Ed. Engl. (2014)

Antiproliferative activity. a) IC50 in A2780 cancer cells and MRC-5 normal lung fibroblasts of 1-py, 1-Cl,6c and CDDP. b) GI50, TGI, and LC50 values (μm) of 1-Cl,7 1-py, and CDDP in the NCI-60 screen. c) Heat map for GI50 values of 1-Cl, 1-py, CDDP, and oxaliplatin (OXA). The deep red color corresponds to the highest activity, whereas the deep blue color represents the lowest activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227564&req=5

fig02: Antiproliferative activity. a) IC50 in A2780 cancer cells and MRC-5 normal lung fibroblasts of 1-py, 1-Cl,6c and CDDP. b) GI50, TGI, and LC50 values (μm) of 1-Cl,7 1-py, and CDDP in the NCI-60 screen. c) Heat map for GI50 values of 1-Cl, 1-py, CDDP, and oxaliplatin (OXA). The deep red color corresponds to the highest activity, whereas the deep blue color represents the lowest activity.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Warwick, Coventry, CV4 7AL (UK).

Show MeSH
Related in: MedlinePlus