Palladium(II) compounds of putrescine and spermine. Synthesis, characterization, and DNA-binding and antitumor properties

Abstract

The reaction of putrescine (Put) with K 2PdCl 4 and PdCl 2 resulted in the synthesis of compounds of formula [PutH 2][PdCl 4] and [Pd 2Cl 4(Put) 2]. Compounds of formula [PdCl 2(SpermH 2)][PdCl 4] and [Pd 2Cl 4(Sperm)] have been also synthesized by reaction of spermine (Sperm) with K 2PdCl 4. The structure of all these compounds has been analyzed by IR and 1H NMR. UV and CD spectroscopic data have shown that all the Pd(II)-polyamine compounds synthesized induce conformational changes in the circular forms of plasmid DNA. Determinations by electrophoresis in agarose gels of the mobility of the DNA in drug:DNA complexes indicated that only the Pdd(II)-putrescine compounds have the ability to induce significant conformational changes in the covalently closed circular (ccc) form of the pUC8 plasmid DNA. The Pdd(II)-putrescine and Pdd(II)-spermine compounds were also assayed for in vitro antiproliferative activity against MDA-MB 468 and HL-60 human cancer cells. The results suggest that the putrescine complexes may be regarded as potential antitumor agents because the ID 50 value of all of the Pdd(II)-putrescine complexes is twofold lower than the ID 50 of cis-DDP. Our data also show that, on the other hand, the Pdd(II)-spermine compounds have low antiproliferative activity.