ABSTRACT
In the present study, an intermediate namely 2-(3-bromopropylamino)-3-chloronaphthalene-1,4-dione was initially synthesized via the nucleophilic addition-elimination reaction between 2,3-dichloro-1,4-naphthoquinone and 3-bromo-1-aminopropane. Then a coupling reaction between the intermediate and piperazine derivatives yielded a number of 1,4-naphthoquinone derivatives. Spectroscopic analysis successfully characterized the products that were obtained in good yields. In vitro antibacterial properties of the compounds were examined against different bacterial strains. In vitro antibacterial properties of the compounds were examined against the bacterial strains S. Aureus, E. Faecalis, E. Coli and P. Aeruginosa. While compound 9 was found to be effective against all bacterial strains used, compound 12 was active against three strains and compounds 10 and 11 were effective against the two. None of the compounds are effective against C. albicans strain. In silico molecular docking studies revealed that all compounds had docking scores comparable to the antibacterial drugs ciprofloxacin and gentamicin and might be considered as DNA gyrase B inhibitors. Molecular dynamics simulations were also conducted for a better understanding of the stability and the selected docked complexes. Additionally, the drug similarity of the synthesized compounds and ADMET characteristics were examined in conjunction with the antibiotic ciprofloxacin, and drug potentials were then evaluated. Compatible predictions were found with the drug similarity and ADMET parameters.
Subject(s)
Escherichia coli , Naphthoquinones , Staphylococcus aureus , Molecular Docking Simulation , Anti-Bacterial Agents/chemistry , Ciprofloxacin/pharmacology , Bacteria , Topoisomerase II Inhibitors/pharmacology , Microbial Sensitivity TestsABSTRACT
Objective: Traumatic brain injury (TBI) is a serious health problem that is related to an increased mortality. In cases of severe TBI, the prediction of prognosis is essential. The enlargement of the optic nerve sheath diameter (ONSD) shows an increased intracranial pressure and is associated with poor outcomes. In this study, we aimed to evaluate the prognostic value of ONSD in patients with severe TBI. Methods: Forty-four patients with severe TBI were retrospectively enrolled in the study. The patients were divided into two groups: survivors (n=17) and non-survivors (n=27). Baseline characteristics, clinical data, Glasgow coma scale (GCS) on hospital admission, brain computed tomography (CT) results, injury severity score (ISS), and Marshall score were recorded for all patients. ONSD was calculated at 3 mm distance from the globe, immediately below the sclera. Results: The ONSD on the initial CT was significantly higher in non-survivors compared with survivors (6.83±1.40 vs. 6.40±1.36, p<0.05). In addition, ISS and Marshall score were significantly higher, whereas GCS was significantly lower in non-survivors. ONSD was positively correlated with Marshall score (r=0.332, p<0.05). Receiver operating characteristics analysis demonstrated that ONSD ≥6.61 had a sensitivity of 70.4% and specificity of 64.7% for predicting mortality. It was shown that ONSD ≥6.61 had a 4.3-fold increased risk for in-hospital mortality (odds ratio: 4.35; 95% confidence interval: 1.195-15.865; p<0.05). Conclusions: The enlargement of ONSD on initial CT was detected to be associated with increased in-hospital mortality in patients with severe TBI.
Subject(s)
Glioblastoma , Humans , Glioblastoma/drug therapy , Interleukin-6/metabolism , Apoptosis , Hypoxia , Piperazines , Cell Line, Tumor , Janus Kinase 2 , STAT3 Transcription FactorABSTRACT
Naringenin is a naturally occurring flavonoid and due to its broad spectrum of biological activities, including anticancer properties, has attracted scientific attention in recent years. To contribute to these studies, we synthesized some new (±)-naringenin cyclic aminoethyl derivatives, analyzed the cytotoxic and anti-proliferative properties of them via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and mitochondrial apoptosis signaling response and gene expressions belong to caspase-3 depended apoptosis as biomarkers in both healthy and cancer cell lines. Our results suggest that some of our naringenin derivatives are potential anticancer agents with a selective death potential and targeting properties for mitochondrial apoptosis signaling against at least human cervix and breast cancer.
