Antibacterial profile and antiproliferative activities over human tumor cells of new silver(I) complexes containing two distinct trifluoromethyl uracil isomers

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Pereira, Gabriele de Menezes ; Nunes, Julia H. Bormio ; Macedo, Vinicius Souza ; Pereira, Douglas Henrique ; Buglio, Kaio Eduardo ; Affonso, Daniele D. ; Ruiz, Ana Lucia T. G. ; de Carvalho, Joao Ernesto ; Frajacomo, Silmara Cristina L. ; Lustri, Wilton R. ; Lima, Carmen Silvia Passos ; Bergamini, Fernando R. G. ; Cuin, Alexandre ; Masciocchi, Norberto ; Corbi, Pedro Paulo

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 262, p. 10-pg., 2024-10-04.

Abstract

New silver(I) complexes of 5-(trifluoromethyl)uracil (5TFMU) and 6-(trifluoromethyl)uracil (6TFMU) isomers were synthesized, characterized, and evaluated as antibacterial and antiproliferative agents. Based on elemental and thermogravimetric analyses, the Ag-5TFMU and Ag-6TFMU species are formulated as AgC5H2F3N2O2 and Ag2C5HF3N2O2, respectively. Infrared and 13C solid-state nuclear magnetic resonance spectroscopies suggest coordination of the trifluoromethyluracil isomers to silver by both nitrogen and oxygen atoms. Confirmation of their structure and connectivity was achieved, in the absence of single crystals of suitable quality, by state-of-theart structural powder diffraction methods. In Ag-5TFMU, the organic ligand is tridentate and two distinct metal coordination environments are found (linear AgN2 as well as C2v AgO4 geometries), whereas Ag-6TFMU contains a complex polymeric structure with tetradentate dianionic 6TFMU moieties and five distinct AgX2 (X = N, O) fragments, further stabilized by ancillary (longer) Ag...O contacts. These species presented modest activity over Gram-positive and Gram-negative bacterial strains, whereas Ag-6TFMU was active over a set of tumor cells, with the best activity over prostate (PC-3) and kidney cell lines and selectivity indices of 4.6 and 1.3, respectively. On the other hand, Ag-5TFMU was active over all considered tumor cells except MCF-7 (breast cancer). The best activity was found for PC-3 cells, but no selectivity was observed. The Ag-5TFMU and Ag-6TFMU species also reduced the proliferation of tongue squamous cell carcinoma cell lines SCC - 4 and SCC-15. Preliminary biophysical assays by circular dichroism suggest that the Ag-5TFMU complex interacts with DNA by intercalation, an effect not seen in Ag-6TFMU. (AU)

• FAPESP's process: 21/10265-8 - Cancer Theranostics Innovation Center (CancerThera)
• Grantee: Carmino Antonio de Souza
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• 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