Tumor inhibiting [1,2-bis(fluorophenyl)ethylenediamine]platinum(II) complexes. Part II: Biological evaluation-in vitro 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" (Cl- 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 approximately equal to 1.6 h) than their R,S configurated analogues (t1/2 approximately equal to 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.
Reile
H
H
Institut für Pharmazie, Lehrstuhl Pharmazeutische Chemie II, Universität Regensburg, Federal Republic of Germany.
Müller
R
R
Gust
R
R
Laske
R
R
Krischke
W
W
Bernhardt
G
G
Spruss
T
T
Jennerwein
M
M
Engel
J
J
Seeber
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D007941:Leukemia P388 / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C064244:(1,2-bis(4-fluorophenyl)ethylenediamine)dichloroplatinum(II); D002945:Cisplatin