title: 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(2)Pt(μ-OH)](2)(NO(3))(2) (L=PMe(3), PPh(3)) in various solvents to give the nucleoside complexes cis-[L(2)Pt{cyt(-H),N(3)N(4)}](3)(NO(3))(3) (L=PMe(3), 1),cis-[L(2)Pt{cyt(-H),N(4)}(cyt,N(3))]NO(3) (L=PPh(3), 2), cis-[L(2)Pt{ado(-H),N(1)N(6)}](2)(NO(3))(2) (L=PMe(3), 3) and cis-[L(2)Pt{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))(2)PtNH=C(R){cyt(-2H)}]NO(3) (R=Me, 5a; R=Ph, 5b) and cis-[(PPh(3))(2)PtNH=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))(2)PtNH=C(R){1-MeCy(-2H)}]NO(3) (R=Me, 7a: R=Ph, 7b), cis-[(PPh(3))(2)PtNH=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.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Padova, Padova, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Montagner
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.forename: Bruno
authors.initials: B
authors.lastname: Longato
mesh_terms: D000241:Adenosine / Q000737:chemistry*; D045744:Cell Line, Tumor; D003562:Cytidine / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008958:Models, Molecular; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D010984:Platinum / Q000737:chemistry*
chemical_list: D009944:Organoplatinum Compounds; D010984:Platinum; D003562:Cytidine; D000241:Adenosine