CYTOTOXICITY AND ANTITUMOR-ACTIVITY OF BIS(PLATINUM) COMPLEXES - A NOVEL CLASS OF PLATINUM COMPLEXES ACTIVE IN CELL-LINES RESISTANT TO BOTH CISPLATIN AND 1,2-DIAMINOCYCLOHEXANE COMPLEXES

The in vitro cytotoxicity and in vivo antitumor activity of bis(platinum) complexes of general formula [L)PtX2-(L))2H2N(CH2)nNH2] (L = NH3, X = Cl or X2 = malonato or where L = py, X = Cl) is reported. Chloride complexes [{PtC12(NH3)}2H2N(CH2)nNH2] may exist as three possible isomers: those containing both coordination units in the cis configuration (2,2/c, c), both coordination units in the trans configuration (2,2/t, t), and the mixed cis, trans species (2,2/c, t), whose synthesis is reported here. The preparation of further complexes with sterically hindered diamine backbones, such as 2,5-dimethyl-2,5-hexanediamine, is exemplified. The biological activity of all complexes were compared. The 2,2/c, c complexes are particularly active in tissue culture in cells resistant both to cisplatin and its 1,2-diaminocyclohexane (dach) analogue. The inhibition of DNA synthesis in L1210/0 cells by the 2,2/c, c complexes is equivalent to that of cisplatin. The presence of at least one cis- [Pt(amine)2] unit appears necessary for activity in cell lines sensitive to cisplatin. © 1990, American Chemical Society. All rights reserved.