Novel bis(carboxylato)dichlorido(ethane-1,2-diamine)platinum(IV) complexes with exceptionally high cytotoxicity.
(OC-6-33)-Dichlorido(ethane-1,2-diamine)dihydroxidoplatinum(IV) (1) was carboxylated using succinic- or 3-methylglutaric anhydride. The resulting bis(carboxylato)platinum(IV) complexes display free, uncoordinated carboxylic acid groups which were further derivatized with primary aliphatic alcohols. The complexes were characterized in detail by elemental analysis, ESI-MS, FT-IR, as well as multinuclear (1H, 13C, 15N, 195Pt) NMR spectroscopy. Cytotoxic properties were evaluated in four human tumor cell lines originating from ovarian carcinoma (CH1, SK-OV-3), cervical carcinoma (HeLa) and colon carcinoma (SW480) by means of the MTT assay (MTT = 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide). Structure-activity relationships showed that the cytotoxicity increased with increasing lipophilicity of the alcoholate moiety yielding IC50 values in the low micromolar or even low nanomolar range.
Reithofer
Michael R
MR
University of Vienna, Institute of Inorganic Chemistry, Waehringer Strasse 42, A-1090 Vienna, Austria. michael.reithofer@univie.ac.at
Schwarzinger
Anne
A
Valiahdi
Seied M
SM
Galanski
Mathea S
MS
Jakupec
Michael A
MA
Keppler
Bernhard K
BK