Cell-permeable lanthanide-platinum(IV) anti-cancer prodrugs.


Journal

Dalton transactions (Cambridge, England : 2003)
ISSN: 1477-9234
Titre abrégé: Dalton Trans
Pays: England
ID NLM: 101176026

Informations de publication

Date de publication:
29 Jun 2021
Historique:
pubmed: 4 6 2021
medline: 15 12 2021
entrez: 3 6 2021
Statut: ppublish

Résumé

Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide-platinum(ii) and lanthanide-platinum(iv) complexes. Luminescence from the europium-platinum(iv) system was quenched, and reduction to platinum(ii) with ascorbic acid resulted in a "switch-on" luminescence enhancement. We used diffusion-based 1H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium-platinum(ii) and gadolinium-platinum(iv) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium-platinum(iv) compared to the gadolinium-platinum(ii) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity.

Identifiants

pubmed: 34080595
doi: 10.1039/d1dt01688a
pmc: PMC8237448
doi:

Substances chimiques

Coordination Complexes 0
Lanthanoid Series Elements 0
Prodrugs 0
Platinum 49DFR088MY
Gadolinium AU0V1LM3JT

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8761-8767

Subventions

Organisme : Wellcome Trust
ID : 201406/Z/16/Z
Pays : United Kingdom

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Auteurs

Kezi Yao (K)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Gogulan Karunanithy (G)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Alison Howarth (A)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Philip Holdship (P)

Department of Earth Sciences, University of Oxford, OX1 3AN, UK.

Amber L Thompson (AL)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Kirsten E Christensen (KE)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Andrew J Baldwin (AJ)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Stephen Faulkner (S)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

Nicola J Farrer (NJ)

Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA, UK. Nicola.Farrer@chem.ox.ac.uk.

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Classifications MeSH