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Starting from the [PtCl(η1-C2H4OMe)(phen)] (phen = 1,10-phenanthroline, 1) platinum(II) precursor, we synthesized and characterized by multinuclear NMR new [Pt(η1-C2H4OMe)(L)(phen)]+ (L = NH3, 2; DMSO, 3) complexes. These organometallic species, potentially able to interact with cell membrane organic cation transporters (OCT), violating some of the classical rules for antitumor activity of cisplatin analogues, were evaluated for their cytotoxicity. Interestingly, despite both complexes 2 and 3 resulting in greater cell uptake than cisplatin in selected tumor cell lines, only 3 showed comparable or higher antitumor activity. General low cytotoxicity of complex 2 in the tested cell lines (SH-SY5Y, SK-OV-3, Hep-G2, Caco-2, HeLa, MCF-7, MG-63, ZL-65) appeared to depend on its stability towards solvolysis in neutral water, as assessed by NMR monitoring. Differently, the [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (3) complex was easily hydrolyzed in neutral water, resulting in a comparable or higher cytotoxicity in cancer cells with respect to cisplatin. Further, both IC50 values and the uptake profiles of the active complex appeared quite different in the used cell lines, suggesting the occurrence of diversified biological effects. Nevertheless, further studies on the metabolism of complex 3 should be performed before planning its possible use in tissue- and tumor-specific drug design.

[Display omitted] • New series of Pt(II) complexes of the type [Pt(η1-CH 2 -CH 2 -OR)(DMSO)(phen)]+ (R = alkyl). • Synthesis of organometallic complexes with the phen and DMSO carrier ligands. • Comparative evaluation of the cytotoxic activity of the new organometallic complexes. The new series of [Pt(η1-CH 2 -CH 2 -OR)(DMSO)(phen)]Cl {R = Me (1b), Et (2b), Pr (3b), Bu (4b), phen = 1,10-phenanthroline} complexes was synthesized starting from the corresponding [PtCl(η1-CH 2 -CH 2 -OR)(phen)] {R = Me (1a), Et (2a), Pr (3a), Bu (4a)} precursors. In the series only complex 1b was previously studied for its potential antitumor activity. In this work, the relative cytotoxicity of 1b - 4b and cisplatin complexes was studied on HeLa, Hep-G2, SH-SY5Y and SK-OV-3 cancer cells. In this way, the effect of R alkyl chain length in modulating cytotoxicity was evidenced. Complex 2b with the Et moiety resulted to be generally more cytotoxic in the tested series of complexes for used cell lines and in particular for the Hep-G2 hepatocarcinoma cells. This approach opens new perspectives for the structural optimization and development of new antitumor drugs. [ABSTRACT FROM AUTHOR]

Starting from the [PtCl(η1-C2H4OMe)(phen)] (phen = 1,10-phenanthroline, 1) platinum(II) precursor, we synthesized and characterized by multinuclear NMR new [Pt(η1-C2H4OMe)(L)(phen)]+ (L = NH3, 2; DMSO, 3) complexes. These organometallic species, potentially able to interact with cell membrane organic cation transporters (OCT), violating some of the classical rules for antitumor activity of cisplatin analogues, were evaluated for their cytotoxicity. Interestingly, despite both complexes 2 and 3 resulting in greater cell uptake than cisplatin in selected tumor cell lines, only 3 showed comparable or higher antitumor activity. General low cytotoxicity of complex 2 in the tested cell lines (SH-SY5Y, SK-OV-3, Hep-G2, Caco-2, HeLa, MCF-7, MG-63, ZL-65) appeared to depend on its stability towards solvolysis in neutral water, as assessed by NMR monitoring. Differently, the [Pt(η1-C2H4OMe)(DMSO)(phen)]+ (3) complex was easily hydrolyzed in neutral water, resulting in a comparable or higher cytotoxicity in cancer cells with respect to cisplatin. Further, both IC50 values and the uptake profiles of the active complex appeared quite different in the used cell lines, suggesting the occurrence of diversified biological effects. Nevertheless, further studies on the metabolism of complex 3 should be performed before planning its possible use in tissue- and tumor-specific drug design. [ABSTRACT FROM AUTHOR]