Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity

Aida M. Basri, Rianne M. Lord, Simon J. Allison, Andrea Rodríguez-Bárzano, Stephanie J. Lucas, Felix D. Janeway, Helena J. Shepherd, Christopher M. Pask, Roger M. Phillips, Patrick C. McGowan

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Abstract

A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.

Original languageEnglish
Pages (from-to)6341-6356
Number of pages16
JournalChemistry - A European Journal
Volume23
Issue number26
Early online date22 Feb 2017
DOIs
Publication statusPublished - 5 May 2017

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Ruthenium
Isomers
Cells
Cisplatin
Ligands
Tumors
picolinamide

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Basri, Aida M. ; Lord, Rianne M. ; Allison, Simon J. ; Rodríguez-Bárzano, Andrea ; Lucas, Stephanie J. ; Janeway, Felix D. ; Shepherd, Helena J. ; Pask, Christopher M. ; Phillips, Roger M. ; McGowan, Patrick C. / Bis-picolinamide Ruthenium(III) Dihalide Complexes : Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity. In: Chemistry - A European Journal. 2017 ; Vol. 23, No. 26. pp. 6341-6356.
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abstract = "A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.",
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Bis-picolinamide Ruthenium(III) Dihalide Complexes : Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity. / Basri, Aida M.; Lord, Rianne M.; Allison, Simon J.; Rodríguez-Bárzano, Andrea; Lucas, Stephanie J.; Janeway, Felix D.; Shepherd, Helena J.; Pask, Christopher M.; Phillips, Roger M.; McGowan, Patrick C.

In: Chemistry - A European Journal, Vol. 23, No. 26, 05.05.2017, p. 6341-6356.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bis-picolinamide Ruthenium(III) Dihalide Complexes

T2 - Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity

AU - Basri, Aida M.

AU - Lord, Rianne M.

AU - Allison, Simon J.

AU - Rodríguez-Bárzano, Andrea

AU - Lucas, Stephanie J.

AU - Janeway, Felix D.

AU - Shepherd, Helena J.

AU - Pask, Christopher M.

AU - Phillips, Roger M.

AU - McGowan, Patrick C.

PY - 2017/5/5

Y1 - 2017/5/5

N2 - A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.

AB - A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2L2] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2L2] complexes but upon a halide exchange reaction to yield [RuI2L2], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2L2] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2L2] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2L2] complexes were found to be more potent than the [RuCl2L2] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.

KW - antitumor agents

KW - cytotoxicity

KW - isomers

KW - ligand effects

KW - ruthenium

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