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

Abstract

a b s t r a c t a r t i c l e i n f o. 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.

trans-Chloridobis[(Z)-1-imino-1-methoxyethane-κN](triphenylphosphane-κP)platinum(II) chloride monohydrate

“…Apart from amines, other neutral ligands such as phosphanes have been exploited and one phosphane compound, the cisplatin analogue cis-Pt(PR 3 ) 2 Cl 2 (R = Me or Ph), has also been widely investigated in relation to its reactivity with nucleobases (Longato et al, 2006). In particular, the mixed phosphane/nucleobase complex cis-bis(triphenylphosphane)-[N-(1-methyl-2-oxo-1,2,3,4-tetrahydropyrimidin-4-ylidene)benzamidine]platinum(II) nitrate exhibits high antitumour activity (Montagner et al, 2011).…”

Synthesis and Evaluation of the Antiproliferative Properties of a Tethered Tubercidin–Platinum(II) Complex

“…[19][20][21][22] known to inhibit the growth of several cancer lines [23][24][25][26] and many of them are clinically used as antiviral drugs. [30][31][32][33] In principle, a platinum complex conjugated to a biologically active nucleoside could combine the reactivity of the platinum center with the pharmacological properties of the nucleoside analogue (e.g., antimetabolite activity or active transmembrane transport). [30][31][32][33] In principle, a platinum complex conjugated to a biologically active nucleoside could combine the reactivity of the platinum center with the pharmacological properties of the nucleoside analogue (e.g., antimetabolite activity or active transmembrane transport).…”

Probing the DNA Reactivity and the Anticancer Properties of a Novel Tubercidin-Pt(II) Complex

“…Numerous classes of Pt(II) compounds have been obtained starting from cisplatin by introducing in the place of the ammonia ligands lipids [ 9 , 10 , 11 ], peptides [ 12 , 13 ], sugars [ 14 , 15 , 16 ], natural products [ 17 ], and some of them have shown interesting anti-proliferative effects. Considering that many anticancer and antiviral drugs currently approved are nucleoside/nucleotide-based [ 18 , 19 , 20 , 21 ], the study of the ligand properties of modified nucleosides and nucleotides towards Pt(II) metal centers is an interesting field in the design of novel anti-neoplastic agents [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. In addition, the involvement of protein transporters located on cellular membranes in the molecular recognition and consequent internalization of nucleosides and nucleotides makes them even more attractive for the design of novel metal-based chemotherapeutics [ 30 ].…”