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

Cytidine (cyt) and adenosine (ado) react with cis-[L2Pt(mu-OH)](2)(NO3)(2) (L=PMe3, PPh3) in various solvents to give the nucleoside complexes cis-[L2Pt{cyt(-H),(NN4)-N-3}](3)(NO3)(3) (L=PMe3, 1), cis-[L2Pt{cyt(-H),N4)(cyt,N)(3))]NO3 (L=PPh3, 2), cis-[L2Pt{ado(-H),(NN6)-N-1}](2)(NO3)(2) (L=PMe3, 3) and cis-[L2Pt{ado(-H),(NN7)-N-6}]NO3 (L= PPh3, 4). When the condensation reaction is carried out in solution of nitrites (RCN, R = Me, Ph) the amidine derivatives cis-[(PPh3)(2)PtNH=C(R){cyt(-2H)}]NO3 (R=Me, 5a; R = Ph, 5b) and cis-[(PPh3)(2)PtNH=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)(2)PtNH=C(R){1-MeCy(-2H)}]NO3 (R = Me, 7a: R = Ph, 7b), cis-[(PPh3)(2)]PtNH=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. (C) 2011 Elsevier Inc. All rights reserved.