Aminophosphine ligands as a privileged platform for development of antitumoral ruthenium(ii) arene complexes.

doi:10.1039/c7dt03369a

Paper

Aminophosphine ligands as a privileged platform for development of antitumoral ruthenium(ii) arene complexes.

Published Nov 28, 2017 · L. M. Broomfield, C. Alonso-Moreno, Eduardo D. Martín

Dalton transactions

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20

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Abstract

The rapid and modular synthesis of the aminophosphine core has been exploited as a tool for rapid development of antitumoral metallodrug candidates. Starting with a series of structurally diverse aminophosphines, all obtained in a single step from commercial amines, a family of Ru(ii)-cymene complexes have been generated and tested in vitro for anti-tumoral activity in a series of cell lines, including the platinum-resistant A2780R. Through this approach, Ru(ii)-aminophosphine complexes have been identified with the IC50 value range as low as 10-0.8 μM. Several biological assays were carried out to gain insight into the mechanism of action. Cell death by apoptosis and pH-independent action has been demonstrated. In addition, a selective cytotoxicity profile for tumoral cells over non-tumoral cells has been identified. Importantly, for the key candidates no loss of activity was observed when applied to the Pt-resistant A2780R, which highlights the potential utility of the bis-phospinoamine scaffold as an easily-tunable auxiliary ligand core in both drug discovery and subsequently a logical design of new anticancer metal-containing drugs. The complexes are characterised by NMR spectroscopy, mass spectrometry and single-crystal X-ray diffraction.

In Vitro Study

Study Snapshot

Aminophosphine ligands show potential as a rapid and modular platform for developing antitumoral ruthenium(ii) arene complexes with low IC50 values and selective cytotoxicity against tumor cells.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Aminophosphine ligands as a privileged platform for development of antitumoral ruthenium(ii) arene complexes.

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References

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Citations

State of the art in organometallic ruthenium metallodrugs for breast cancer treatment: Advances and innovations

Organometallic ruthenium metallodrugs show promise as promising alternatives to platinum derivatives for breast cancer treatment, with potential applications in combination therapy, phototherapy, and nanotechnology.

Evaluation of heteroscorpionate ligands as scaffolds for the generation of Ruthenium(II) metallodrugs in breast cancer therapy.

Heteroscorpionate-based metallodrugs show potential as an alternative to platinum therapy for breast cancer therapy, with RUSCO-2 showing high cytotoxic activity in TNBC cell lines and a stable structure-activity relationship.

Synthesis, structure and biological evaluation as antibacterial agents of Ru(II)-p-cymene-aryldicyclohexylphosphine complexes

Both Ru(II)-p-cymene-aryldicyclohexylphosphine complexes show potential antibacterial effects, with 2 showing higher bacterial growth inhibition activity compared to 1, possibly due to its molecular structure.

Enhanced Antitumoral Activity of Encapsulated BET Inhibitors When Combined with PARP Inhibitors for the Treatment of Triple-Negative Breast and Ovarian Cancers

Encapsulated BET inhibitor JQ1 in nanoparticles enhances the antitumoral activity of PARP inhibitors in treating BRCA1/2 cancers, potentially overcoming resistance and enhancing their effectiveness.

Design and Anticancer Properties of New Water-Soluble Ruthenium–Cyclopentadienyl Complexes

New water-soluble ruthenium-cyclopentadienyl complexes show promising anticancer properties, with micromolar and submicromolar IC50 values in various cancer cell lines.