A new complex of silver(I) with probenecid: Synthesis, characterization, and studies of antibacterial and extended spectrum β-lactamases (ESBL) inhibition activities

• Autor(a) principal: Lustri, Wilton R.
• Data de Publicação: 2023
• Outros Autores: Lazarini, Silmara C., Simei Aquaroni, Nayara Ap., Resende, Flávia A., Aleixo, Nadia A., Pereira, Douglas H., Lustri, Bruna Cardinali [UNESP], Moreira, Cristiano Gallina [UNESP], Ribeiro, Camila M. [UNESP], Pavan, Fernando R. [UNESP], Nakahata, Douglas H., Gonçalves, Adriano M. [UNESP], Nascimento-Júnior, Nailton M. [UNESP], Corbi, Pedro P.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• DOI: 10.1016/j.jinorgbio.2023.112201
• Texto Completo: http://dx.doi.org/10.1016/j.jinorgbio.2023.112201; http://hdl.handle.net/11449/248615
• topic: Antibacterial agent; Molecular docking; Multi-drug resistant; Probenecid; Silver complex; β-lactamase inhibition

This article describes the in vitro antibacterial and β-lactamase inhibition of a novel silver(I) complex with the sulfonamide probenecid (Ag-PROB). The formula Ag2C26H36N2O8S2·2H2O for the Ag-PROB complex was proposed based on elemental analysis. High-resolution mass spectrometric studies revealed the existence of the complex in its dimeric form. Infrared, nuclear magnetic resonance spectroscopies and Density Functional Theory calculations indicated a bidentate coordination of probenecid to the silver ions by the oxygen atoms of the carboxylate. In vitro antibacterial activities of Ag-PROB showed significant growth inhibitory activity over Mycobacterium tuberculosis, S. aureus, and P. aeruginosa PA01biofilm-producers, B. cereus, and E. coli. The Ag-PROB complex was active over multi-drug resistant of uropathogenic E. coli extended spectrum β-lactamases (ESBL) producing (EC958 and BR43), enterohemorrhagic E. coli (O157:H7) and enteroaggregative E. coli (O104:H4). Ag-PROB was able to inhibit CTX-M-15 and TEM-1B ESBL classes, at concentrations below the minimum inhibitory concentration for Ag-PROB, in the presence of ampicillin (AMP) concentration in which EC958 and BR43 bacteria were resistant in the absence of Ag-PROB. These results indicate that, in addition to ESBL inhibition, there is a synergistic antibacterial effect between AMP and the Ag-PROB. Molecular docking results revealed potential key residues involved in interactions between Ag-PROB, CTX-M-15 and TEM[sbnd]1B, suggesting the molecular mechanism of the ESBL inhibition. The obtained results added to the absence of mutagenic activity and low cytotoxic activity over non-tumor cell of the Ag-PROB complex open a new perspective for future in vivo tests demonstrating its potential of use as an antibacterial agent.