Mechanistic and cytotoxicity studies of group IV β-diketonate complexes

R.M. Lord, J.J. Mannion, A.J. Hebden, A.E. Nako, B.D. Crossley, M.W. McMullon, F.D. Janeway, R.M. Phillips, P.C. McGowan

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Group IV metal complexes have previously shown promise as novel anticancer agents. Here, we discuss the mechanistic and cytotoxic nature of a series of group IV β-diketonate coordination complexes. Clear evidence that the ligands are exchangeable on the metal centre and that the β-diketonate ligands can act as potential drug delivery vehicles of the group IV metal ions was obtained. When evaluated for the cytotoxicity against human colon adenocarcinoma (HT-29) and human breast adenocarcinoma (MCF-7) cell lines, a general trend of decreasing potency down the group IV metals was observed. The most promising results obtained were for the hafnium complexes, with the tris diphenyl β-diketonate hafnium complex exhibiting IC50 values of 4.9±0.9 μM and 3.2±0.3 μM against HT-29 and MCF-7, respectively, which are comparable with the activity of cisplatin against the same cell lines. This tri β-diketonate hafnium complex is the first to show potent in vitro cytotoxic activity. The results reported show that ligand design has a significant effect on the cytotoxic potential of the complexes, and that these group IV complexes warrant further evaluation as novel metal-containing anticancer agents. Transition to toxicity: A series of asymmetric and symmetric group IV complexes have been synthesised and evaluated as potential cytotoxic agents. Solution NMR studies were undertaken to understand the drugs exchange/fluxional properties. Among the agents evaluated is the first hafnium tris-β-diketonate complex to show potent in vitro cytotoxic activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
LanguageEnglish
Pages1136-1139
Number of pages4
JournalChemMedChem
Volume9
Issue number6
Early online date29 Apr 2014
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

Fingerprint

Hafnium
Cytotoxicity
Metals
Coordination Complexes
Ligands
Antineoplastic Agents
Adenocarcinoma
Cells
Cell Line
MCF-7 Cells
Cytotoxins
Drug delivery
Pharmaceutical Preparations
Cisplatin
Inhibitory Concentration 50
Metal ions
Toxicity
Colon
Breast
Nuclear magnetic resonance

Cite this

Lord, R. M., Mannion, J. J., Hebden, A. J., Nako, A. E., Crossley, B. D., McMullon, M. W., ... McGowan, P. C. (2014). Mechanistic and cytotoxicity studies of group IV β-diketonate complexes. ChemMedChem, 9(6), 1136-1139. https://doi.org/10.1002/cmdc.201402019
Lord, R.M. ; Mannion, J.J. ; Hebden, A.J. ; Nako, A.E. ; Crossley, B.D. ; McMullon, M.W. ; Janeway, F.D. ; Phillips, R.M. ; McGowan, P.C. / Mechanistic and cytotoxicity studies of group IV β-diketonate complexes. In: ChemMedChem. 2014 ; Vol. 9, No. 6. pp. 1136-1139.
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Lord, RM, Mannion, JJ, Hebden, AJ, Nako, AE, Crossley, BD, McMullon, MW, Janeway, FD, Phillips, RM & McGowan, PC 2014, 'Mechanistic and cytotoxicity studies of group IV β-diketonate complexes', ChemMedChem, vol. 9, no. 6, pp. 1136-1139. https://doi.org/10.1002/cmdc.201402019

Mechanistic and cytotoxicity studies of group IV β-diketonate complexes. / Lord, R.M.; Mannion, J.J.; Hebden, A.J.; Nako, A.E.; Crossley, B.D.; McMullon, M.W.; Janeway, F.D.; Phillips, R.M.; McGowan, P.C.

In: ChemMedChem, Vol. 9, No. 6, 06.2014, p. 1136-1139.

Research output: Contribution to journalArticle

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AU - Hebden, A.J.

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AB - Group IV metal complexes have previously shown promise as novel anticancer agents. Here, we discuss the mechanistic and cytotoxic nature of a series of group IV β-diketonate coordination complexes. Clear evidence that the ligands are exchangeable on the metal centre and that the β-diketonate ligands can act as potential drug delivery vehicles of the group IV metal ions was obtained. When evaluated for the cytotoxicity against human colon adenocarcinoma (HT-29) and human breast adenocarcinoma (MCF-7) cell lines, a general trend of decreasing potency down the group IV metals was observed. The most promising results obtained were for the hafnium complexes, with the tris diphenyl β-diketonate hafnium complex exhibiting IC50 values of 4.9±0.9 μM and 3.2±0.3 μM against HT-29 and MCF-7, respectively, which are comparable with the activity of cisplatin against the same cell lines. This tri β-diketonate hafnium complex is the first to show potent in vitro cytotoxic activity. The results reported show that ligand design has a significant effect on the cytotoxic potential of the complexes, and that these group IV complexes warrant further evaluation as novel metal-containing anticancer agents. Transition to toxicity: A series of asymmetric and symmetric group IV complexes have been synthesised and evaluated as potential cytotoxic agents. Solution NMR studies were undertaken to understand the drugs exchange/fluxional properties. Among the agents evaluated is the first hafnium tris-β-diketonate complex to show potent in vitro cytotoxic activity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Lord RM, Mannion JJ, Hebden AJ, Nako AE, Crossley BD, McMullon MW et al. Mechanistic and cytotoxicity studies of group IV β-diketonate complexes. ChemMedChem. 2014 Jun;9(6):1136-1139. https://doi.org/10.1002/cmdc.201402019