Synthesis, characterization and cytotoxic properties of platinum(II) complexes containing the nucleosides adenosine and cytidine

Cytidine (cyt) and adenosine (ado) react with cis-[L2Pt(μ-OH)]2(NO3)2 (L = PMe3, PPh3) in various solvents to give the nucleoside complexes cis-[L2Pt{cyt(− H),N3N4}]3(NO3)3 (L = PMe3, 1),cis-[L2Pt{cyt(− H),N4}(cyt,N3)]NO3 (L = PPh3, 2), cis-[L2Pt{ado(− H),N1N6}]2(NO3)2 (L = PMe3, 3) and cis-[L2Pt{ado(− H),N6N7}]NO3 (L = PPh3, 4). When the condensation reaction is carried out in solution of nitriles (RCN, R = Me, Ph) the amidine derivatives cis-[(PPh3)2PtNH=C(R){cyt(− 2H)}]NO3 (R = Me, 5a; R = Ph, 5b) and cis-[(PPh3)2PtNH=C(R){ado(− 2H)}]NO3 (R = Me, 6a: R = Ph, 6b) are quantitatively formed. The coordination mode of these nucleosides, characterized in solution by multinuclear NMR spectroscopy and mass spectrometry, is similar to that previously observed for the nucleobases 1-methylcytosine (1-MeCy) and 9-methyladenine (9-MeAd). The cytotoxic properties of the new complexes, and those of the nucleobase analogs, cis-[(PPh3)2PtNH=C(R){1-MeCy(− 2H)}]NO3 (R = Me, 7a: R = Ph, 7b), cis-[(PPh3)2PtNH=C(R){9-MeAd(− 2H)}]NO3 (R = Me, 8a: R = Ph, 8b) have been investigated in a wide panel of human cancer cells. Interestingly, whereas the Pt(II) nucleoside complexes (1–4) did not show appreciable cytotoxicity, the corresponding amidine derivatives (7a, 7b, 8a, 8b, 5b, and 6b) exhibited a significant in vitro antitumor activity.

The azametallacycle complexes cis-[L2PtNH=C(R){Nucl(− 2H)}]NO3 (L = PPh3; R = Me, Ph: Nucl = 1-methylcytosine, cytidine, 9-methyladenine and adenosine) exhibit a significant cytotoxic activity toward different human tumor cell lines.Figure optionsDownload as PowerPoint slide