Abstract
Although the antimicrobial potency of the pyrazole nucleus is widely reported, the antimicrobial effects of the 2-(4-bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4), found to be active against several other conditions, have never been investigated. Considering the worldwide need for new antimicrobial agents, we thought it noteworthy to assess the minimum inhibitory concentration (MICs) of BBB4 but, due to its scarce water-solubility, unequivocal determinations were tricky. To obtain more reliable MICs and to obtain a substance also potentially applicable in vivo, we recently prepared water-soluble, BBB4-loaded dendrimer nanoparticles (BBB4-G4K NPs), which proved to have physicochemical properties suitable for clinical application. Here, with the aim of developing a new antibacterial agent based on BBB4, the BBB4-G4K NPs were tested on several strains of different species of the Staphylococcus genus. Very low MICs (1.5–3.0 µM), 15.5–124.3-fold lower than those of the free BBB4, were observed against several isolates of S. aureus and S. epidermidis, the most pathogenic species of this genus, regardless of their resistance patterns to antibiotics. Aiming at hypothesizing a clinical use of BBB4-G4K NPs for staphylococcal skin infections, cytotoxicity experiments on human keratinocytes were performed; it was found that the nano-manipulated BBB4 released from BBB4-G4K NPs (LD50 138.6 µM) was 2.5-fold less cytotoxic than the untreated BBB4 (55.9 µM). Due to its physicochemical and biological properties, BBB4-G4K NPs could be considered as a promising novel therapeutic option against the very frequent staphylococcal skin infections.
Highlights
Introduction iationsOver the past twenty years, the number of multidrug-resistant bacteria (MDR) has grown exponentially [1]
The same goes for MRSA colonization in nonsurgical wounds such as traumatic wounds, burns, and chronic ulcers, for which no conclusive evidence has been found about the best antibiotic regimen to treat the MRSA colonization [50]
Imagining that BBB4 could be a good candidate as a new antibacterial agent, we examined its antibacterial activity on the strains, including the MDR, representative of species both Gram-positive and Gram-negative
Summary
As for staphylococci, they are a group of bacteria that include more than 30 species. The same goes for MRSA colonization in nonsurgical wounds such as traumatic wounds, burns, and chronic ulcers (i.e., the diabetic ulcer, pressure ulcer, arterial insufficiency ulcer, and venous ulcer), for which no conclusive evidence has been found about the best antibiotic regimen to treat the MRSA colonization [50] In this alarming scenario, made of missing epidemiologic evidence, a plethora of uncertainties, due to the interindividual responses of patients to existing antibiotics, and of a decreasing efficacy of available drugs, the development of new curative options against MRSA infections is urgent. Physicochemical characteristics, could be advisable for biomedical applications Such NPs have proven to be selectively active against different species of the Staphylococcus genus, and to be able to inhibit their growth whatever their resistance to methicillin or their resistance to existing antibiotics, amoxicillin and linezolid included. BBB4-G4K NPs may represent a possible new therapeutic option for addressing the severe staphylococcal infections caused by MDR species, which are of increasing concern around the world
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