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

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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.
Original languageEnglish
Pages (from-to)1136-1139
Number of pages4
JournalChemMedChem
Volume9
Issue number6
Early online date29 Apr 2014
DOIs
Publication statusPublished - Jun 2014
Externally publishedYes

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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