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

ABSTRACT: NMR-based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ¹-C₂H₄OMe)(DMSO)(phen)]⁺ (phen = 1,10-phenanthroline), Pt-EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt-EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular against the neuroblastoma cell line (SH-SY5Y). In this study, the mechanism of action of Pt-EtOMeSOphen on SH-SY5Y cells was investigated using ¹H NMR-based metabolomics and compared with cisplatin. The observed time response of SH-SY5Y cells under treatment revealed a faster action of Pt-EtOMeSOphen compared with cisplatin, with a response already observed after six hours of exposure, suggesting a cytosolic target. NMR-based metabolomics demonstrated a peculiar alteration of the glutathione metabolism pathway and the diacylglycerol expression.

SUBMITTER: De Castro F

PROVIDER: S-EPMC9205715 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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

De Castro Federica F Stefàno Erika E De Luca Erik E Muscella Antonella A Marsigliante Santo S Benedetti Michele M Fanizzi Francesco Paolo FP

Bioinorganic chemistry and applications 20220610

NMR-based metabolomics is a very effective tool to assess the tumor response to drugs by providing insights for their mode of action. Recently, a novel Pt(II) complex, [Pt(ƞ1-C2H4OMe)(DMSO)(phen)]+ (phen = 1,10-phenanthroline), Pt-EtOMeSOphen, was synthesized and studied for its antitumor activity against eight human cancer cell lines. Pt-EtOMeSOphen showed higher cytotoxic effects than cisplatin in most of the cancer cell lines and in particular agai ...[more]

PMID: 35721691

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Project description:The electrochemistry and photophysics of the Pt(II) complexes [Pt(naphen)(X)] (Hnaphen = naphtho[1,2-b][1,10]phenanthroline, X = Cl or C≡CPh) containing the rigid tridentate C^N^N-coordinating pericyclic naphen ligand was studied alongside the complexes of the tetrahydro-derivative [Pt(thnaphen)(X)] (Hthnaphen = 5,6,8,9-tetrahydro-naphtho[1,2-b][1,10]phenanthroline) and the N^C^N-coordinated complex [Pt(bdq)(Cl)] (Hbdq = benzo[1,2-h:5,4-h']diquinoline. The cyclic voltammetry showed reversible reductions for the C^N^N complexes, with markedly fewer negative potentials (around -1.6 V vs. ferrocene) for the complexes containing the naphen ligand compared with the thnaphen derivatives (around -1.9 V). With irreversible oxidations at around +0.3 V for all of the complexes, the naphen made a difference in the electrochemical gap of about 0.3 eV (1.9 vs. 2.2 eV) compared with thnaphen. The bdq complex was completely different, with an irreversible reduction at around -2 V caused by the N^C^N coordination pattern, which lacked a good electron acceptor such as the phenanthroline unit in the C^N^N ligand naphen. Long-wavelength UV-Vis absorption bands were found around 520 to 530 nm for the C^N^N complexes with the C≡CPh coligand and were red-shifted when compared with the Cl derivatives. The N^C^N-coordinated bdq complex was markedly blue-shifted (493 nm). The steady-state photoluminescence spectra showed poorly structured emission bands peaking at around 630 nm for the two naphen complexes and 570 nm for the thnaphen derivatives. The bdq complex showed a pronounced vibrational structure and an emission maximum at 586 nm. Assuming mixed 3LC/3MLCT excited states, the vibronic progression for the N^C^N bdq complex indicated a higher LC character than assumed for the C^N^N-coordinated naphen and thnaphen complexes. The blue-shift was a result of the different N^C^N vs. C^N^N coordination. The photoluminescence lifetimes and quantum yields ΦL massively increased from solutions at 298 K (0.06 to 0.24) to glassy frozen matrices at 77 K (0.80 to 0.95). The nanosecond time-resolved study on [Pt(naphen)(Cl)] showed a phosphorescence emission signal originating from the mixed 3LC/3MLCT with an emission lifetime of around 3 µs.

Dataset Information

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

Publications

A NMR-Based Metabolomic Approach to Investigate the Antitumor Effects of the Novel [Pt(<i>η</i> <sup>1</sup>-C<sub>2</sub>H<sub>4</sub>OMe)(DMSO)(phen)]<sup>+</sup> (phen = 1,10-Phenanthroline) Compound on Neuroblastoma Cancer Cells.

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