Linear gold(I) complex with tris-(2-carboxyethyl)phosphine (TCEP): Selective antitumor activity and inertness toward...

The search for modulating ligand substitution reaction in gold complexes is essential to find new active metallo compounds for medical applications. In this work, a new linear and hydrosoluble gold^I complex with tris-(2-carboxyethylphosphine) (AuTCEP). The two phosphines coordinate linearly to the metal as solved by single crystal X-ray diffraction. Complete spectroscopic characterization is also reported. In vitro growth inhibition (GI₅₀) in a panel of nine tumorigenic and one non-tumorigenic cell lines demonstrated the complex is highly selective to ovarium adenocarcinoma (OVCAR-03) with GI₅₀ of 3.04 nmol mL^-1. Moreover, non-differential uptake of AuTCEP was observed between OVCAR-03 (tumor) and HaCaT (non-tumor) two cell lines. Biophysical evaluation with the sulfur-rich biomolecules showed the compound does not interact with two types of zinc fingers, bovine serum albumin, N-acetyl-l-cysteine and also l-histidine, revealing to be inert to ligand substitution reactions with these molecules. However, AuTCEP demonstrated to cleave plasmidial DNA, suggesting DNA as a possible target. No antibacterial activity was observed in the strains evaluated. Besides, it inhibits 15% of the activity of a mixture of serine-β-lactamase and metallo-β-lactamase from Bacillus cereus in the enzymatic activity assay, similarly to EDTA. These results suggest AuTCEP is selective to metallo-β-lactamase but the cell uptake is hindered, and the compound does not reach the periplasmic space of Gram-positive bacteria. The unique inert behavior of AuTCEP is interesting and represent the modulation of the reactivity through coordination chemistry to decrease the toxicity associated with Au^I complexes and its lack of specificity, generating very selective compounds with unexpected targets.