Abstract
The emergence of resistant bacterial strains mainly due to misuse of antibiotics has seriously affected our ability to treat bacterial illness, and the development of new classes of potent antimicrobial agents is desperately needed. In this study, we report the efficient synthesis of a new pyrazoline-pyridine containing ligand L1 which acts as an NN-donor for the formation of a novel silver (I) complex 2. The free ligand did not show antibacterial activity. High potency was exhibited by the complex against three Gram-negative bacteria, namely Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumanii with the minimum inhibitory concentration (MIC) ranging between 4 and 16μg/mL (4.2-16.7μM), and excellent activity against the fungi Candida albicans and Cryptococcus neoformans (MIC ≤ 0.25μg/mL = 0.26μM). Moreover, no hemolytic activity within the tested concentration range was observed. In addition to the planktonic growth inhibition, the biofilm formation of both Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa was significantly reduced by the complex at MIC concentrations in a dose-dependent manner for Pseudomonas aeruginosa, whereas a biphasic response was obtained for MRSA showing that the sub-MIC doses enhanced biofilm formation before its reduction at higher concentration. Finally, complex 2 exhibited strong DNA binding with a large drop in DNA viscosity indicating the absence of classical intercalation and suggesting the participation of the silver ion in DNA binding which may be related to its antibacterial activity. Taken together, the current results reveal that the pyrazoline-pyridine silver complexes are of high interest as novel antibacterial agents, justifying further in vitro and in vivo investigation.
Highlights
Nowadays the preparation of novel antibacterial agents has become a priority because of the presence of multidrug-resistant pathogens (WHO factsheet 2018)
The current results reveal that the pyrazoline-pyridine silver complexes are of high interest as novel antibacterial agents, justifying further in vitro and in vivo investigation
Chemical shifts are reported in ppm relative to DMSO-d6 (1H: d = 2.50 ppm, 13C: d = 39.52 ± 0.06 ppm) and atom numbering for the ligand L1 is available in the ESI
Summary
Nowadays the preparation of novel antibacterial agents has become a priority because of the presence of multidrug-resistant pathogens (WHO factsheet 2018). The biological activity of metal complexes has, attracted increasing research interest over the years. The antibacterial, antifungal, and antiviral properties of silver ions, silver compounds, and, recently, silver nanoparticles have been extensively studied (Liang et al 2018). Even though silver ions are considered potent and safe, they are quickly reduced to metallic silver Ag° in the skin from the action of reducing agents, like thiols (Dabrowiak 2017). An effective way to control this extensive reduction is to react silver ions with a metal chelating moiety of an organic ligand resulting in a silver complex of desired physical, chemical, and/or biological properties able to ‘‘release’’ the silver ions to the medium
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