Mechanistic and cytotoxicity studies of group IV β-diketonate complexes.
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.
Chemistry Department, University of Leeds, Woodhouse Lane, Leeds, West Yorkshire, LS2 9JT (UK).
Rianne M
RM
Lord
James J
JJ
Mannion
Andrew J
AJ
Hebden
Adi E
AE
Nako
Benjamin D
BD
Crossley
Max W
MW
McMullon
Felix D
FD
Janeway
Roger M
RM
Phillips
Patrick C
PC
McGowan
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006195:Hafnium / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D061986:MCF-7 Cells; D008968:Molecular Conformation
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D002945:Cisplatin; D006195:Hafnium
anticancer agents; cytotoxicity; group IV; metal complexes; metals in medicine