Synthesis and Evaluation of the Cytotoxic Activity of Water-Soluble Cationic Organometallic Complexes of the Type [Pt(η1-C2H4OMe)(L)(Phen)]+ (L = NH3, DMSO; Phen = 1,10-Phenanthroline)

Abstract

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.

A NMR‐Based Metabolomic Approach to Investigate the Antitumor Effects of the Novel [Pt(η1‐C2H4OMe)(DMSO)(phen)]+ (phen = 1,10‐Phenanthroline) Compound on Neuroblastoma Cancer Cells

“…All solvents and reagents were purchased from Aldrich Chemical Company and used as received, except otherwise stated. Cisplatin, cis-[PtCl 2 (NH 3 ) 2 ], and Pt-EtOMeSOphen were synthesized according to previously reported procedures and gave satisfactory analytical data [29,30].…”

“…In the present study, a 1 H NMR metabolomic analysis of cell lysates (aqueous and lipid extracts) and their growth media was performed to study the metabolic effects of Pt-EtOMeSOphen treatment on SH-SY5Y cells. e cells were treated (for 6, 12, and 24 h) with Pt-EtOMeSOphen 50 μM, concentration corresponding to the IC 50 value for SH-SY5Y cells at 24 h [29]. Moreover, a further parallel assay with cisplatin using the same experimental setup and design (the cisplatin IC 50 value and same times of cells treatment) was performed.…”

“…e cytotoxic activity of Pt-EtOMeSOphen has been evaluated on different cancer cells lines (SH-SY5Y, SK-OV-3, Hep-G2, Caco-2, HeLa, MCF-7, MG-63, ZL-55), showing a higher cytotoxicity compared with cisplatin in many of the tested cell lines and in particular against the neuroblastoma cell line SH-SY5Y. Moreover, we have recently demonstrated that Pt-EtOMeSOphen is able to inhibit SH-SY5Y cancer cells' survival, motility, and invasion [29].…”

“…In these contexts, we have recently reported the synthesis and the cytotoxic activity of a novel Pt(II) organometallic complex of the type [Pt(ƞ 1 -C 2 H 4 OMe)(DMSO)(phen)] + (Pt-EtOMeSOphen) (Figure 1) [29].…”

Two out of Three Musketeers Fight against Cancer: Synthesis, Physicochemical, and Biological Properties of Phosphino CuI, RuII, IrIII Complexes

“…Thanks to the experience gained, alternative strategies have been developed that have led to the synthesis of numerous organometallic platinum-based compounds such as carboplatin and nedaplatin, with the aim of developing selectively toxic molecules towards cancer cells, hoping to generate an efficient bio-distribution and an inability to develop resistance conditions [6]. For this purpose, the correlation between the activity of the metal and its chemical environment is fundamental, in fact, the possibility of using a wide range of ligands paves the way for the study of new and different mechanisms of action, which is capable of limiting the general toxicity associated with these drugs while, in the meantime, maximizing the efficiency of cellular uptake [7][8][9][10][11]. In recent years, the research has underlined how a synthetic approach of this type allows great progress in the synthesis and optimization of competitive chemotherapy; however, the intrinsic reactivity and biological characteristics of platinum make it difficult to overcome many important therapeutic obstacles and the consequent achievement of an ideal pharmacology.…”