Platinum alkynyl complexes: Cellular uptake, inhibition of thioredoxin reductase and toxicity in zebrafish embryos

[Display omitted] •Mono-alkynyl platinum(II) complexes have a lower cellular uptake than bis-alkynyl platinum(II) complexes.•Platinum(II) alkynyl complexes are good TrxR inhibitors.•Toxicity studies in zebrafish embryos indicated a suitable therapeutic index. Cytotoxic platinum(II) alkynyl complexes...

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Bibliographic Details
Published in:Inorganica Chimica Acta 2019-09, Vol.495, p.118982, Article 118982
Main Authors: Schur, Julia, Lüning, Anna, Klein, Axel, Köster, Reinhard W., Ott, Ingo
Format: Article
Language:English
Subjects:
Alkynyl complexes
Cellular uptake
Embryos
Platinum
Reductases
Thioredoxin reductase
Toxicity
Zebrafish
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Summary:[Display omitted] •Mono-alkynyl platinum(II) complexes have a lower cellular uptake than bis-alkynyl platinum(II) complexes.•Platinum(II) alkynyl complexes are good TrxR inhibitors.•Toxicity studies in zebrafish embryos indicated a suitable therapeutic index. Cytotoxic platinum(II) alkynyl complexes of the type [(COD)Pt(Me)(C≡CR)] and [(COD)Pt(C≡CR)2] were evaluated for their cellular uptake, thioredoxin reductase (TrxR) inhibition and toxicity against zebrafish embryos. Quantification of the cellular uptake confirmed lower accumulation levels for the mono-alkynyl derivatives [(COD)Pt(Me)(C≡CR)] in comparison to the bis-alkynyl complexes [(COD)Pt(C≡CR)2]. Importantly, the complexes were efficient inhibitors of TrxR in contrast to cisplatin, which was not active. Toxicity studies in zebrafish showed lower activity if compared with the cytotoxicity against tumor cells indicating a suitable therapeutic index for the complexes.
ISSN:0020-1693
1873-3255
DOI:10.1016/j.ica.2019.118982