Cytotoxicity of asymmetric platinum complexes against L-1210 cells. Effect of bulky substituents.

Abstract

The asymmetric platinum complexes cis-Pt(LL')Cl2 (L = NH3, L' = CH3NH2, (CH3)2NH, C2H5NH2 and (C2H5)2NH and LL' = N,N-dimethylethylenediamine),--one of the NH3 groups of cis-Pt(NH3)2Cl2 was substituted by alkylamine--, were synthesized and their cytotoxic effects have been measured using L-1210 cells. The IC50 values of the asymmetric platinum complexes,--being obtained after 24 h exposure of L-1210 cells to the platinum complexes--, are almost comparable to the corresponding value of cis-Pt(NH3)2Cl2. In 2 h exposure, however, the IC50 values of the platinum complexes were dramatically changed, i.e., a marked difference was observed between those of L' = RNH2 and L' = R2NH. On the other hand, the amounts of platinum taken into the L-1210 cells is little affected by the alkylamino substitution. The results suggest that the bifunctional platinum binding to the target molecule may be responsible for the cytotoxicity.