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

Abstract

Cytidine (cyt) and adenosine (ado) react with cis-[L 2Pt(μ-OH)] 2(NO 3) 2 (L = PMe 3, PPh 3) in various solvents to give the nucleoside complexes cis-[L 2Pt{cyt(− H), N 3 N 4 }] 3(NO 3) 3 (L = PMe 3, 1) , cis-[L 2Pt{cyt(− H), N 4 }(cyt, N 3 )]NO 3 (L = PPh 3, 2), cis-[L 2Pt{ado(− H), N 1 N 6 }] 2(NO 3) 2 (L = PMe 3, 3) and cis-[L 2Pt{ado(− H), N 6 N 7 }]NO 3 (L = PPh 3, 4). When the condensation reaction is carried out in solution of nitriles (RCN, R = Me, Ph) the amidine derivatives cis-[(PPh 3) 2PtNH=C(R){cyt(− 2H)}]NO 3 (R = Me, 5a; R = Ph, 5b) and cis-[(PPh 3) 2PtNH=C(R){ado(− 2H)}]NO 3 (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-[(PPh 3) 2PtNH=C(R){1-MeCy(− 2H)}]NO 3 (R = Me, 7a: R = Ph, 7b), cis-[(PPh 3) 2PtNH=C(R){9-MeAd(− 2H)}]NO 3 (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.