Synthesis, characterization and cytotoxic properties of platinum(II) complexes containing the nucleosides adenosine and cytidine |
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Authors: | Montagner Diego Gandin Valentina Marzano Cristina Longato Bruno |
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Affiliation: | a Dipartimento di Scienze Chimiche, Università di Padova, Via Marzolo 1, 35131-Padova, Italyb Dipartimento di Scienze Farmaceutiche, Università di Padova, Via Marzolo 5, 35131-Padova, Italy |
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Abstract: | 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. |
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Keywords: | Nucleosides complexes of platinum(II) Cytidine Adenosine Nitrile insertion Cytotoxicity |
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