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Structural and solution chemistry, antiproliferative effects, and serum albumin binding of three pseudohalide derivatives of auranofin

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A Correction to this article was published on 19 November 2019

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Abstract

Three pseudohalide analogues of the established gold drug auranofin (AF hereafter), of general formula Au(PEt3)X, i.e. Au(PEt3)CN, Au(PEt3)SCN and Au(PEt3)N3 (respectively denoted as AFCN, AFSCN and AFN3), were prepared and characterized. The crystal structure was solved for Au(PEt3)SCN highlighting the classical linear geometry of the 2-coordinate gold(I) center. The solution behaviour of the compounds was then comparatively analysed through 31PNMR providing evidence for an acceptable stability under physiological-like conditions. Afterward, the reaction of these gold compounds with bovine serum albumin (BSA) and consequent adduct formation was investigated by 31PNMR. For all the studied gold compounds, the [Au(PEt3)]+ moiety was identified as the reactive species in metal/protein adducts formation. The cytotoxic effects of the complexes were subsequently measured in comparison to AF against a representative colorectal cancer cell line and found to be still relevant and roughly similar in the three cases though far weaker than those of AF. These results show that the nature of the anionic ligand can modulate importantly the pharmacological action of the gold-triethylphosphine moiety, affecting the cytotoxic potency. These aspects may be further explored to improve the pharmacological profiles of this family of metal complexes.

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Change history

  • 19 November 2019

    In the initial online publication, the given name of the first author was incorrectly displayed and should have read Damiano. The original article has been corrected and the proper representation of the authors’ names and their affiliation is also listed here.

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Acknowledgements

D.C. gratefully acknowledge Associazione Italiana per la Ricerca sul Cancro for the financial support (AIRC 1-year Fellowship for Italy—Project Code: 22294). L.M. gratefully acknowledges AIRC (Associazione Italiana per la Ricerca sul Cancro) and ECRF (Ente Cassa di Risparmio di Firenze) for the financial support (AIRC-ECRF19650). CIRCMSB and ente CRF are also acknowledged. T.M. thanks University of Pisa (Rating Ateneo 2018/2019) for the financial support.

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Correspondence to Damiano Cirri or Luigi Messori.

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The original version of this article was revised: the given name of the first author has been corrected.

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Cirri, D., Fabbrini, M.G., Massai, L. et al. Structural and solution chemistry, antiproliferative effects, and serum albumin binding of three pseudohalide derivatives of auranofin. Biometals 32, 939–948 (2019). https://doi.org/10.1007/s10534-019-00224-1

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