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

Author(s)

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

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-the-art 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 C_2v 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.

Organisation(s)

Department of Inorganic Chemistry

External organisation(s)

Universidade Estadual de Campinas, Federal University of Tocantins, Instituto Tecnológico de Aeronáutica, University of Araraquara, Universidade Federal de Uberlândia, Federal University of Juiz de Fora, Università degli Studi dell'Insubria

Journal

Journal of Inorganic Biochemistry

Volume

262

ISSN

0162-0134

DOI

https://doi.org/10.1016/j.jinorgbio.2024.112752

Publication date

01-2025

Peer reviewed

Yes

Austrian Fields of Science 2012

106002 Biochemistry, 104003 Inorganic chemistry

Keywords

ASJC Scopus subject areas

Biochemistry, Inorganic Chemistry

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Portal url

https://ucrisportal.univie.ac.at/en/publications/ea7f6640-d961-46ef-874a-1d6e2f8e4b83