Synthesis of Au(I) bis-N-heterocyclic carbene-oxaliplatin-gemcitabine triple-action anticancer prodrug

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2022-05

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Platinum- and gold-based compounds have emerged as promising anticancer agents. Pt(IV) prodrugs are more stable than their Pt(II) counterparts and, with the flexibility provided by the two additional axial ligands, are able to be structurally fine-tuned. These features make Pt(IV) compounds a great platform for overcoming systemic toxicity and drug resistance issues characteristic of Pt(II) compounds and for preparing multi-action anticancer drugs. Gold(I) bis-N-heterocyclic carbenes (Au(I) bis-NHCs) are able to localize specifically in mitochondria and inhibit the activity of thioredoxin reductase (TrxR); this renders them both good mitochondria-targeting agents and potent antitumor agents. However, there has been no record in the literature of coupling these two powerful anticancer compounds. Here, we report the synthesis of a conjugate comprising an Au(I) bis-NHC, oxaliplatin, and gemcitabine. A synergistic effect between the gold and the platinum component was inferred from preliminary results in the cell proliferation experiments. Further investigations will be needed to elucidate and characterize the putative synergism and other biological properties.

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