Stability and cellular studies of [rac-1,2-bis(4-fluorophenyl)ethylenediamine][cyclobutane-1,1-dicarboxylato]platinum(II), a novel, highly active carboplatin derivative

Abstract

The synthesis of the diastereomeric [1,2-bis(4-fluorophenyl)ethylendiamine][cyclobutane-1,1-dicarboxylato]platinum(II) complexes, rac- and meso-4F-Pt(CBDC), the evaluation of their structures, their tumor-inhibiting properties and their stability in physiol. environment were described (ref. complexes: the dichloro- and sulfatoplatinum(II) analogs, carboplatin and cisplatin). Rac-4F-Pt(CBDC) equaled cisplatin and surpassed carboplatin in its effect on human breast cancer cell lines (MCF-7 and MDA-MB-231). Rac-4F-Pt(CBDC) was largely insensitive against attack of nucleophiles (Cl-). In vitro studies on the binding of rac-4F-Pt(CBDC) to albumin showed that the non-protein-bound fraction was comparable to that of carboplatin. The distinctly better anti-breast cancer activity of rac-4F-Pt(CBDC) than of carboplatin was attributed to its ability to accumulate in the tumor cells. The human ovarian cancer cell line NIH-OVCAR-3 was also strongly inhibited by rac-4F-Pt(CBDC).