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

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Pereira, Gabriele de Menezes ; Nunes, Julia H. Bormio ; Cruz, Allefe B. ; Pereira, Douglas Henrique ; Buglio, Kaio Eduardo ; Ruiz, Ana Lucia T. G. ; de Carvalho, Joao Ernesto ; Frajacomo, Silmara Cristina L. ; Lustri, Wilton R. ; Bergamini, Fernando R. G. ; Corbi, Pedro Paulo

• Document type: Journal article
• Source: JOURNAL OF FLUORINE CHEMISTRY; v. 266, p. 9-pg., 2023-02-01.

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 center dot H2O. Infrared (FT-IR) and solid-state C-13 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 mu mol L-1. Further studies are necessary to confirm efficiency and safety for continuing the pre-clinical evaluation of the Ag-5FC complex. (AU)

• FAPESP's process: 21/08717-8 - Synthesis of copper, silver and gold complexes involving nucleotide analogues in the search of new alternatives for the treatment of ovarian cancer
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/07458-9 - Use of varied nutrient sources and agro-industrial residues in the production of bacterial cellulose for topical application as a support for sustained release of (metal) antibacterial and antitumor drugs
• Grantee: Wilton Rogério Lustri
• Support Opportunities: Regular Research Grants