Synthesis, characterization, crystal structure and in vitro antiproliferative assays of the 2-thiouracilato(triphenylphosphine)gold(I) complex

• Published in: Journal of molecular structure 2019-02, Vol.1178, p.169-178
• Main Authors: Bormio Nunes, Julia H., Simoni, Deborah A., Braga, Lúcia E.O., Ruiz, Ana Lúcia T.G., Ernesto de Carvalho, João, Corbi, Pedro P.
• Format: Article
• Language: English
• Subjects: 2-Thiouracil; Antiproliferative assays; Crystal structure; Gold(I); Triphenylphosphine; Tumor cells
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2018.10.026

A gold(I) complex with triphenylphosphine and 2-thiouracil, named 2-thiouracilato(triphenylphosphine)gold(I) (Ph3P-Au-tuH), was synthesized and characterized by a set of chemical and spectroscopic techniques. By elemental and mass spectrometric (ESI-QTOF-MS) analyses, the molecular formula AuC22H18N2OSP was proposed, corresponding to a 1:1 metal/ligand composition. Spectroscopic studies based on the infrared (IR) and nuclear magnetic resonance (NMR) of 1H, 13C and 31P evidenced the conversion of the chlorido(triphenylphosphine)gold(I) into the 2-thiouracilato(triphenylphosphine)gold(I), with substitution of Cl− by thiouracil. The crystal structure of the Ph3P-Au-tuH complex was determined by single crystal X-ray diffraction and shows the coordination of 2-thiouracil to gold(I) by the thiol group. Further, the in vitro antiproliferative assays of the 2-thiouracilato(triphenylphosphine)gold(I) complex showed its high activity when compared to the chlorido(triphenylphosphine)gold(I) one against lung (NCI-H460) and colon (HT29) tumor cell lines, with total growth inhibition (TGI) values of 26.7 and 28.5 μg mL−1, respectively, and also high selectivity towards tumor cells when compared to the normal cell line (HaCat). In addition, the Ph3P-Au-tuH complex showed a TGI value lower than 0.25 μg mL−1 for the leukemia cell line (K-562) with a selectivity index (SI) of 24.4, exhibiting a better in vitro cytotoxicity and selectivity than doxorubicin against this specific cell. Synthesis, structural characterization and antiproliferative assays of the 2-thiouracilato(triphenylphosphine)gold(I) complex over a panel of tumor cells are presented in this manuscript. [Display omitted] •A phosphinegold(I) complex with 2-thiouracil is presented.•Crystal structure shows the coordination of thiouracil to gold by the thiol group.•Elemental and mass spectrometric analyses indicate a 1:1 metal/ligand composition.•The complex presented antiproliferative activities over a panel of tumor cells.•The best activity was over K-562 leukemia cell line with TGI