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

Author(s)

Gomes, S. Q. ^[1] ; Vitoriano, L. ^[1] ; de Arruda, E. G. R. ^[1] ; Ruiz, A. L. T. G. ^{[2, 3]} ; Candido, T. ^[2] ; de Carvalho, J. E. ^{[2, 3]} ; Lustri, W. R. ^[4] ; Abbehausen, C. ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, POB 6154, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, UNICAMP, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, BR-13148218 Paulinia, SP - Brazil

^[3] Univ Estadual Campinas, UNICAMP, Fac Pharmaceut Sci, BR-13083871 Campinas, SP - Brazil

^[4] Univ Araraquara, UNIARA, BR-14801340 Araraquara, SP - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 186, p. 104-115, SEP 2018.
• Web of Science Citations: 3

Abstract

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 (GI(50)) in a panel of nine tumorigenic and one non-tumorigenic cell lines demonstrated the complex is highly selective to ovarium adenocarcinoma (OVCAR-03) with GI(50) 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-beta-lactamase and metallo-beta-lactamase from Bacillus cereus in the enzymatic activity assay, similarly to EDTA. These results suggest AuTCEP is selective to metallo-beta-lactarnase 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. (AU)

• FAPESP's process: 15/09833-0 - Sustainable delivery system based on biocellulose/metallic complexes containing bioactive ligands
• Grantee: Wilton Rogério Lustri
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/12719-0 - Fighting bacterial resistance: metal complexes and the metallo-beta-lactamases inhibition
• Grantee: Camilla Abbehausen
• Support Opportunities: Regular Research Grants