Antitumor activity of gold(i), silver(i) and copper(i) complexes containing chiral tertiary phosphines.
The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC(50) values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino) ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)- and (R(*),R(*))-1,2-phenylenebis(methylphenylphosphine); and (R,R)-, (S,S)- and (R(*),R(*))-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CH1cisR and SKOV-3 tumour models. IC(50) values in the range 0.01 - 0.04 muM were determined for the most active compounds, silver(I) complexes of the tetra(tertiary phosphine). Furthermore, the chirality of the ligand appeared to have little effect on the overall activity of the complexes: similar IC(50) data were obtained for complexes of a particular metal ion with each of the stereoisomeric forms of a specific ligand.
McKeage
M J
MJ
Department of Pharmacology and Clinical Pharmacology Faculty of Medicine and Health Services The University of Auckland Private Bag 92019 Auckland New Zealand.
Papathanasiou
P
P
Salem
G
G
Sjaarda
A
A
Swiegers
G F
GF
Waring
P
P
Wild
S B
SB