Synthesis and antitumor activity of [1,2-bis(4-fluorophenyl)ethylenediamine][dicarboxylato]platinum(II) complexes

The synthesis of the diastereomeric [1,2-bis(4-fluorophenyl)ethylenediamine][dicarboxylato]platinum(II) complexes, rac- and meso-4F-Pt(X) [X = oxalato (Ox), malonato (Mal), hydroxymalonato (OHMal), phenylmalonato (PhMal), tetrahydro-4H-pyran-4,4-dicarboxylato (Thpdc)], the evaluation of their structure, water soly., resistance against attack by nucleophiles, and growth inhibiting properties on the human MCF-7 breast cancer cell line are described [parent compds.: rac-4F-Pt(CBDC), and meso-4F-Pt(CBDC); ref. complexes: carboplatin, cisplatin, rac- and meso-4F-PtCl2]. The most active 4F-Pt(X) complexes, rac-4F-Pt(Mal), rac-4F-Pt(OHMal), and rac-4F-Pt(Thpdc), equal the parent compd. rac-4F-Pt(CBDC) as well as cisplatin and surpass carboplatin in their effect on the MCF-7 breast cancer cell line. Their water soly., which is of importance for an application in the cancer chemotherapy, is higher than that of rac-4F-Pt(CBDC), esp. in the case of rac-4F-Pt(OHMal) and rac-4F-Pt(Thpdc). In comparison to the dichloroplatinum(II) analog (4F-PtCl2) the stability of the 3 compds. in the presence of the strong nucleophile iodide is markedly enhanced, which means a redn. of the protein bound drug fraction in the blood and tissue compartments accompanied by an increase of the active, free drug level. The found physiochem. properties of these compds. meet the requirements for the transferability of their promising breast cancer inhibiting effects detected in cell culture expts. to in vivo conditions