Characterization studies and cytotoxicity assays of Pt(II) and Pd(II) dithiocarbamate complexes by means of FT-IR, NMR spectroscopy and mass spectrometry.
The precursors [M(ESDTM)Cl(2)] (M=Pt(II), Pd(II); ESDTM=EtO(2)CCH(2)(CH(3))NCS(2)Me, S-methyl(ethylsarcosinedithiocarbamate)) were synthesized as previously reported [J. Inorg. Biochem. 83 (2001) 31] and used to obtain [M(ESDT)Cl](n) (ESDT=ethylsarcosinedithiocarbamate anion) species. The complexes formed through reaction between [M(ESDT)Cl](n) and the two chiral amino-alcohols synephryne (Syn) and norphenylephrine (Nor) have been synthesized, with the ultimate goal of preparing mixed dithiocarbamate/amino metal complexes of the type [M(ESDT)(Am)Cl] (Am=Syn, Nor). These compounds have been isolated, purified and characterized by means of FT-IR, mono- and bidimensional NMR spectroscopy and mass spectrometry ESI/MS (electronspray mass spectra). The experimental data suggest that in all cases coordination of the dithiocarbamate ligand (ESDT) takes a place through the two sulfur atoms, the -NCSS moiety acting as a symmetrical bidentate chelating group, in a square-planar geometry around the M(II) ion, while the other two coordination positions are occupied by the chlorine atom and the amino-alcohol ligand, respectively. In particular, synephrine and norphenylephrine appear to be bound to the metal atom through the amino nitrogen atom by means of a dative bond. Finally, the biological activity of the new complexes has been studied by MTT (tetrazolio salt reduction) test and by detecting the inhibition of DNA synthesis and of clonal growth in various cancer cell lines. All Pd(II) derivatives showed a noticeable activity very close to that of cisplatin, used as reference drug. Moreover, they showed significantly reduced cross-resistance to cisplatin in a pair of cell lines (2008/C13*) with known acquired cisplatin resistance mechanisms.
Alverdi
V
V
Department of Inorganic, Metallorganic and Analytical Chemistry, University of Padua, via Loredan 4, 35131 Padua, Italy.
Giovagnini
L
L
Marzano
C
C
Seraglia
R
R
Bettio
F
F
Sitran
S
S
Graziani
R
R
Fregona
D
D
D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D010165:Palladium / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D009944:Organoplatinum Compounds; D013859:Thiocarbamates; D010165:Palladium; D004247:DNA