Add time:07/20/2019         Source:sciencedirect.com

Meso-configurated [1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-4-PtX2) with SO42−, NO3−, PhSO3− cyclobutane-1,1-dicarboxylate (CBDC) and isocitrate as the leaving groups (X) and the two diastereomeric dichloroplatinum(II) derivatives were synthesized. The influence of the leaving groups of meso-4-PtX2 on several murine tumors: P388 leukemia, MXT-M3.2 breast cancer (hormone-sensitive) and MXT-Ovex breast cancer (hormone-insensitive) was studied. The compounds with leaving groups, which are more easily exchangeable by water molecules (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 cisplatin. The MXT-Ovex breast cancer, however, was strongly inhibited by meso-4-PtSO4 which was even more active than cisplatin. The hormone-sensitive MXT-M3.2 breast cancer underwent 78% inhibition by the most interesting compound of the meso-4-PtX2 leaving-group series (ie meso-4-PtCl2) at the non-toxic dosage of 5 μmol/kg. With the well-tolerated, more active diastereomer, d,l-4-PtCl2, 99% inhibition of tumor growth could be achieved at a dose of 10 μmol/kg.

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