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The A22 is a chemical compound that acts as a reversible inhibitor of a bacterial cell wall protein MreB leading the rods to the coccoid form. Thus, by changing the bacterial form, many properties can be affected, as the acquisition of nutrients, cell division, the clamping surfaces, motility and pathogenesis. Infections caused by strains of Pseudomonas aeruginosa have great clinical importance because these microorganisms can include more than one resistance mechanism acting together, limiting treatment options. Thus, it is important to investigate the action of A22 against P. aeruginosa, once there are urgent needs for new antimicrobial compounds for increase the arsenal therapeutic to treat diseases caused by this microrganism. Therefore, this study investigated for the first time the antimicrobial activity of A22 against seve standards strains of Gram negative microorganisms and twenty-eight clinical isolates of P. aeruginosa. This study performed an additional investigation to analyze the cyto and genotoxic potential effects from A22 on human peripheral blood mononuclear cells (PBMCs). The antibacterial activity of A22 was studied by broth microdilution method and time-kill assay. The cytotoxicity was evaluated by MTT assay at 24, 48 and 72 h of exposure to A22 and the genotoxicity was evaluated by the Comet assay. The susceptibility tests showed A22 has a relevant antibacterial activity against P. aeruginosa, including multidrug-resistant (MDR) clinical isolates. The A22 treatment not showed genotoxic effects against PBMCs in almost all concentrations tested at 24 and 48 h of exposure. Only for concentration of 32 μg/mL (highest tested) the damage index was significantly higher in all moments. The MTT assay demonstrated that A22 was able to maintain cell viability in all exposure times. In summary, the A22 demonstrated important anti-Pseudomonas activity and showed no cyto and genotoxic significant effect. These results need to be considered in future in vitro and in vivo studies in order to introduce the A22 as a possible therapeutic option.

(2016) Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells, Pharmaceutical Biology, 54:12, 2968-2977, DOI: 10.1080/13880209.2016 Context: Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment.Objective: The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells. Materials and methods: NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model. Results: Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately. Discussion and conclusion: Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.ARTICLE HISTORY

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