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

  • Damiano CirriEmail author
  • Maria Giulia Fabbrini
  • Lara Massai
  • Serena Pillozzi
  • Annalisa Guerri
  • Alessio Menconi
  • Luigi MessoriEmail author
  • Tiziano Marzo
  • Alessandro Pratesi


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.


Metal based drugs NMR Cancer Protein metalation BSA 



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.

Supplementary material

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Supplementary material 1 (DOCX 371 kb)


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Copyright information

© Springer Nature B.V. 2019
corrected publication 2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of FlorenceSesto FiorentinoItaly
  2. 2.Department of Experimental and Clinical MedicineUniversity of FlorenceFlorenceItaly
  3. 3.Department of PharmacyUniversity of PisaPisaItaly
  4. 4.Department of Chemistry and Industrial ChemistryUniversity of PisaPisaItaly

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