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

Abstract

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.

Synthesis and in vitro antitumor activity of novel iridium(III) complexes with enantiopure C2-symmetrical vicinal diamine ligands

“…25,26 Particularly, it has been reported that optically pure (1,2-diarylethane-1,2-diamine)dichloroplatinum(II) complexes induce significant inhibitory effects on the growth of leukemic and tumor cells, and a distinctly better effect was generally observed with the R,R/S,S configurations compared with the R,S counterparts. [27][28][29][30] These results motivated us to apply the findings from platinum(II) complexes to iridium(III) complexes. In this manuscript, we report the synthesis of novel dichlorobis[enantiopure 1,2-diarylethane-1,2-diamine]iridium(III) chlorides (general formula see Graphic Abstract) and their antiproliferative effects on a panel of representative human solid tumor cell lines.…”

The Relation Between Stereochemistry and Biological Activity of Platinum(II) Complexes Chelated with Chiral Diamine Ligands: An Intricate Problem

“…Protection against nucleophilic attack can be achieved by using molecular modelling techniques to generate a shield effect around the platinum atom. This protection due to the steric hindrance of the ligand has been put forward to explain the lower reactivity of compound (19a) towards reactive biological compounds [113]. However, it has to be kept in mind that avoiding these undesirable reactions could also result in a negative effect on binding to DNA, leading to less active complexes.…”

Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and specific platinum accumulation

“…1. [14,18,24,25]. Despite the ionic nature of the diaqua(1,2-diphenylethylenediamine)platinum(II) sulfates, their water solubility is quite low because of the contribution of the large, hydrophobic neutral ligand.…”