Oral Anticancer Heterobimetallic PtIV−AuI Complexes Show High In Vivo Activity and Low Toxicity

Tomer Babu, Hiba Ghareeb, Uttara Basu, Hemma Schueffl, Sarah Theiner, Petra Heffeter*, Gunda Koellensperger*, Norman Metanis*, Valentina Gandin*, Ingo Ott*, Claudia Schmidt*, Dan Gibson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


AuI-carbene and PtIV−AuI-carbene prodrugs display low to sub-μM activity against several cancer cell lines and overcome cisplatin (cisPt) resistance. Linking a cisPt-derived PtIV(phenylbutyrate) complex to a AuI-phenylimidazolylidene complex 2, yielded the most potent prodrug. While in vivo tests against Lewis Lung Carcinoma showed that the prodrug PtIV(phenylbutyrate)-AuI-carbene (7) and the 1 : 1 : 1 co-administration of cisPt: phenylbutyrate:2 efficiently inhibited tumor growth (≈95 %), much better than 2 (75 %) or cisPt (84 %), 7 exhibited only 5 % body weight loss compared to 14 % for 2, 20 % for cisPt and >30 % for the co-administration. 7 was much more efficient than 2 at inhibiting TrxR activity in the isolated enzyme, in cells and in the tumor, even though it was much less efficient than 2 at binding to selenocysteine peptides modeling the active site of TrxR. Organ distribution and laser-ablation (LA)-ICP-TOFMS imaging suggest that 7 arrives intact at the tumor and is activated there.

Original languageAmerican English
Article numbere202217233
JournalAngewandte Chemie - International Edition
Issue number10
StatePublished - 1 Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.


  • Au-Carbene
  • Heterbimetallic
  • Multi-Targeting
  • Prodrugs
  • Pt


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