Synthesis, characterization and in vitro biological assays of a silver(I) complex with 5-fluorouracil: A strategy to overcome multidrug resistant tumor cells

Abstract A silver(I) complex with the antitumor drug 5-fluorouracil was synthesized and characterized by a set of chemical and spectroscopic techniques. Elemental, thermogravimetric and mass spectrometric analyses indicate a 3:2 metal/ligand composition, with minimal formula Ag 3 (C 4 HFN 2 O 2 )(C 4 H 2 FN 2 O 2 ). Solid-state NMR and IR spectroscopic studies suggest that coordination to silver(I) occurs by the nitrogen atoms N1 and N3, and by oxygen atom O2 of the ligand. The in vitro antiproliferative assays show the higher activity of the silver(I) complex with 5-fluorouracil when compared to the free drug against ovarian multidrug resistant (NCI/ADR-RES) and colon (HT29) tumor cell lines, with 50% growth inhibition (GI 50 ) values of 0.36 and 0.34 μg mL −1 , respectively. Gel electrophoresis assay indicated that the silver(I) complex does not interact with pIRES DNA plasmid. The compound also presented higher activity than cisplatin against a variety of tumor cell lines. The compound was also assayed over Gram-positive ( Staphyloccocus aureus ) and −negative ( Escherichia coli and Pseudomonas aeruginosa ) bacterial strains and the MIC values show its activity over the considered microorganisms at high concentrations.