TUMOR-INHIBITING [1,2-BIS(FLUOROPHENYL)ETHYLENEDIAMINE]PLATINUM(II) COMPLEXES .2. BIOLOGICAL EVALUATION - INVITRO STUDIES ON THE P-388 D1 LEUKEMIA-CELL LINE

Experiments on the P 388 D1 cell line (48 h exposure) demonstrate that [1,2‐bis‐(fluorophenyl)ethylenediamine]platinum(II) complexes are comparably active on the cell number and 3H‐thymidine incorporation, irrespective of the position of the fluorine atom (ortho, meta, or para) and the nature of the “leaving group” (C1− or H2O). However, the compounds of the R,R/S,S series are more active than those of the R,S series and comparable to cisplatin. In the “tumor colony forming assay” the R,R/S,S configurated compounds are about ten times as active as cisplatin. The R,R/S,S configurated diaqua[1,2‐bis(4‐fluorophenyl)ethylenediamine]platinum(II) salts reach their half maximum effect more readily (t1/2 ≅ 1.6 h) than their R,S configurated analogues (t1/2 ≅ 20 h). A time limited contact of the cells with R,R/S,S configurated diaqua[1,2‐bis(4‐fluorophenyl)ethylenediamine]platinum(II) salts (∼1h) leads to a similar inhibition like a permanent drug exposure indicating a fast uptake of the complex by the tumor cell. In experiments on the Ehrlich ascites tumor of the mouse and on the L 1210 leukemia cell line R,R/S,S‐[1,2‐bis(4‐fluorophenyl)ethylenediamine]dichloroplatinum(II) turns out to be equipotent with cisplatin. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim