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

This article describes the in vitro antibacterial and ß-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 ß-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 TEM1B, 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.

Antibacterial activities and antiproliferative assays over a tumor cells panel of a silver complex with 4-aminobenzoic acid: Studies in vitro of sustained release using bacterial cellulose membranes as support.

The aims of this work were to evaluate the antibacterial and antiproliferative potential in vitro of the metal complex with 4-aminobenzoic acid (Ag-pABA) and a drug delivery system based on bacterial cellulose (BC-Ag-pABA). The Ag-pABA complex was characterized by elemental analysis, high resolution mass spectrometry and single-crystal X-ray diffraction techniques, which indicated a 1:2 metal/pABA composition plus a nitrate ion coordinated to silver by the oxygen atom, with the coordination formula [Ag (C7H7NO2)2(NO3)]. The coordination of pABA to the silver ion occurred by the nitrogen atom. The in vitro antibacterial activity of the complex evaluated by minimum inhibitory concentration assays demonstrated the effective growth inhibitory activity against Gram-positive, Gram-negative biofilm producers and acid-alcohol resistant Bacillus. The antiproliferative activities against a panel of eight tumor cells demonstrated the activity of the complex with a significant selectivity index (SI). The DNA interaction capacity and the Ames Test indicated the absence of mutagenicity. The BC-Ag-pABA composite showed an effective capacity of sustained release of Ag-pABA. The observed results validate further studies on its mechanisms of action and the conditions that mediate the in vivo biological effects using animal models to confirm its safety and effectiveness for treatment of skin and soft tissues infected by bacterial pathogens, urinary tract infections and cancer.