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 succinicor 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 (H-1, C-13, N-15, Pt-195) 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. (C) 2008 Elsevier Inc. All rights reserved.