Synthesis, spectroscopic characterization, antibacterial activity and antiproliferative profile of a new silver(I) complex of 5-fluorocytosine

Abstract

In this paper, we report the synthesis, structural characterization, and explore the potential antibacterial and antiproliferative activities of a new silver(I) complex of the nucleotide analogue 5-fluorocytosine, Ag-5FC. Elemental and thermogravimetric (TGA) analyses led to the minimal formula AgC4H4FN3O·H2O. Infrared (FT-IR) and solid-state 13C nuclear magnetic resonance (NMR) spectroscopic analyses indicate that the ligand coordinates to the metal ion by its nitrogen and oxygen atoms. High resolution mass spectrometric (HRMS) data confirmed the proposed composition of the complex as well as the presence of recombination species in solution. Molecular modeling reinforces the proposed N,O-coordination of 5FC to silver as indicated by IR data with a possible structure of the complex in a dimeric form, of coordination formula [Ag(C4H4FN3O)(OH2)]2. The complex showed a modest antimicrobial activity (MIC = 4.3 mmol⋅L−1) against Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus cereus) strains. Despite the low solubility, the Ag-5FC complex totally inhibited the proliferation of colon (HT-29), multidrug resistant ovarian (NCI/ADR-RES), prostate (PC-3), and renal (786–0) tumor cell lines in a concentration range of 6.2 to 9.3 µmol L−1. Further studies are necessary to confirm efficiency and safety for continuing the pre-clinical evaluation of the Ag-5FC complex.