Breast cancer-inhibiting properties of leaving group derivatives of [1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]platinum(II)

Abstract

Meso-PtLX2 (I; L = 1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine; X = 0.5SO4, NO3, PhSO3, cyclobutane-1,1-dicarboxylate (CBDC), isocitrate) and the 2 diastereomeric PtLCl2 were prepd. The influence of the leaving groups of I on several murine tumors: P388 leukemia, MTX-M3.2 breast cancer (hormone-sensitive) and MXT-Ovex breast cancer (hormone-insensitive) was studied. The compds. with leaving groups, which are more easily exchangeable by H2O mols. (SO42-, NO3-, PhSO3-, produced stronger tumor inhibition and also more pronounced side effects than those with moderately stable (Cl-) or stable (CBDC, isocitrate) bond leaving groups. Against the P388 leukemia, none of the tested complexes were cytotoxic to the same extent as cis-Pt(NH3)2Cl2 (II). The MXT-Ovex breast cancer, however, was strongly inhibited by meso-PtLSO4 which was even more active than II. The hormone-sensitive MXT-M3.2 breast cancer underwent 78% inhibition by the most interesting compd. of I leaving-group series (i.e. meso-PtLCl2) at the nontoxic dosage of 5 micro mol/kg. With the well-tolerated, more active diastereomer, D,L-PtLCl2, 99% inhibition of tumor growth could be achieved at a dose of 10 micro mol/kg.