Synthèse des diastéréoisomères 1,2-bis(2-,3- et 4-fluorophényl)éthylènediamines 4–6, 10–12 à partir de méso 1,2-bis(2-hydroxyphényl)éthylènediamine et de 2-,3- et 4-fluorobenzaldéhyde par la transposition de diaza-Cope et leur transformation en complexes [1,2-bis(2-,3- et 4-fluorophényl)éthylènediamine]dihaloplatine (II) (Hal = Cl: 13–18; Hal = I: 19–24) à l'aide de K2PtHaI4

Abstract

The synthesis of the diastereomeric 1,2-bis(2-,3-and 4-fluorophenyl)ethylenediamines 4-6, lo-12 from meso-1,2-bis(2-hydroxyphenyl)ethylenediamine and 2-, 3-and 4-fluorobenzaldehyde by a diaza-Cope-rearrangement and their conversion into the [1,2-bis(2-, 3-and 4-fluorophenyl)ethylenediamine]dihaloplatinum (II) complexes (Hal = Cl, 13-M; Hal = I, 19-24) with K,PtHal, is described. From the diiodoplatinum(I1) complexes (19-24) the better water soluble diaqua[l,Zbis(2-, 3-and 4-fluorophenyl)ethylenediamine]platinum(II) sulfates (25-30) and [1,2-bis(4fluorophenyl)ethylenediamine]dinitratoplatinum (II) complexes (31 and 32) are obtained by reacting with Ag2S04 or AgNOs. On the P388Di leukemia cell line the racemic platinum (II) complexes are more active than their meso-analogues and equiactive with cis-platin. The position of the fluorine atom and the kind of the leaving group do not influence the activity. RbumC-Synthese des diastCrkoisomi%res 1,2-bis(2-,3-et 4-fluoroph&yl)6thyl&nediamines 4-6, lo-12 g partir de m&o 1,2-bis(2-hydroxyphCnyl)&hyl&nediamine et de 2-,3-et 4-fluorobenzaldbhyde par la transposition de diaza-Cope et leur transformation en complexes [1,2-bis(2-,3-et 4-fluorophCnyl)6thylkwdi~e]dihaIoplatine (II) (Hal = Cl: 13-18; Hal = I: 19-24) g I'aide de K,PtH&. A partir des complexes de diiodoplatine (ZZ) (19-24), on obtient des composes plus hydrosolubles tels des sulfates de diaquaplatine (ZZ) [I,2-bis(Juoro-2,-3 et 4 phenyl)tthylenediamine] (25-30) et des [1,2-bis(4-fluorophenyl) tthylenediamine]dinitratoplatine (ZZ) complexes (31 et 32) par reaction avec Ag2S04 et AgN03 respectivement. Dans les cellules en lignees de leucemie P388Dt, les complexes racemiques de platine (ZZ) sont plus actifs que leurs analogues meso et aussi actifs que le cis-platine. La position du jluor et la nature du groupe partant n'influencent pas l'activite. diastereomeric l,%bis(2-,3-and 4-fluorophenyl)ethylenediamines / d&a-Cope-rearrangement / [1,2-bis(2-,3-and 4luoropbenyl)ethylenediamine] dihaIopIatinum(I1) complexes / diaqua[l,Zbis(2-,3-and 4-fluorophenyl)ethylenediamine] platinum(II) spits / P388D1 leukemia cell line/structure activity-relationship

[N-Ethyl- and [N,N‘-Diethyl-1,2-bis(2,6-difluoro-3-hydroxyphenyl)- ethylenediamine]dichloroplatinum(II): Structure and Cytotoxic/Estrogenic Activity in Breast Cancer Cells

“…First hints to this mode of action of [1,2-diarylethylenediamine]platinum(II) complexes, with which we have thoroughly investigated the influence of substituents in the aromatic rings on their antitumor activity, ,,,− ,− came from a study with [ meso -1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) ( meso -6-PtLL ‘), [ meso - and [ d,l -1,2-bis(4-fluorophenyl)ethylendiamine]platinum(II) ( meso - and d , l -8-PtLL ‘) and cisplatin (cDDP) . In experiments on the human MCF-7 breast cancer cell line, the rate of complexation with DNA followed the order d , l -8-PtLL ‘ > cDDP > meso -8-PtLL ‘ > meso -6-PtLL ‘.…”

Mono- and Polynuclear [Alkylamine]platinum(II) Complexes of [1,2-Bis(4-fluorophenyl)ethylenediamine]platinum(II): Synthesis and Investigations on Cytotoxicity, Cellular Distribution, and DNA and Protein Binding

“…Remarkable activity of polynuclear compounds was noticed in a wide panel of tumor cells, but for breast cancer cell lines, especially the MCF-7 cell line, a relatively low activity was found. , Therefore, we focused our attention to the design of drugs with increased selectivity for breast tumors. In this initial study, we combined the well-known [1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) complex , with alkylamines, alkyldiamines, and the DAB(PA) 4 polyimine dendrimer. We studied the significance of the charge and the alkyl chain length of the molecules on their cytotoxicity, the cellular uptake, the nuclear content, the binding to DNA in cells, and the binding characteristics to human serum albumin (HSA).…”