Nitazoxanide potentiates linezolid against linezolid-resistant Staphylococcus aureus in vitro and in vivo.

BACKGROUND: Antimicrobial resistance is a growing menace, claiming millions of lives all over the world. In this context, drug repurposing is one approach gaining interest as a suitable alternative to conventional drug discovery and development. METHODS: Whole-cell assays were used to screen FDA-approved drugs to identify novel antimicrobial agents active against bacterial pathogens. Following identification of nitazoxanide, its various characteristics, such as antimicrobial activity against MDR isolates, time-kill kinetics, ability to synergize with approved drugs, antibiofilm activity and ability to generate resistance in Staphylococcus aureus, were determined, followed by determination of its in vivo potential against MDR S. aureus. RESULTS: Nitazoxanide demonstrated a potent in vitro antistaphylococcal profile, including equipotent activity against clinical drug-resistant S. aureus and Enterococcus spp. Nitazoxanide exhibited concentration-dependent killing, significantly eradicated preformed S. aureus biofilm and S. aureus did not generate resistance to it. Nitazoxanide strongly synergized with linezolid both in vitro and in vivo against linezolid-susceptible and -resistant S. aureus, displaying superior activity to untreated control and drug-alone treatment groups. CONCLUSIONS: Nitazoxanide can be utilized in combination with linezolid against infections caused by linezolid-resistant S. aureus as it exhibits strong synergism in vitro and in vivo.

Synthesis of Solution-Processable Donor-Acceptor Pyranone Dyads for White Organic Light-Emitting Devices.

A series of donor-acceptor pyranones (3a-m, 4a-h) were synthesized using α-oxo-ketene- S, S-acetal as the synthon for their application as emissive materials for energy-saving organic light-emitting devices (OLEDs). Among them, five pyranones 3f, 3g, 3h, 3m, and 4e exhibited highly bright fluorescence in the solid state and weak or no emission in the solution state. Photophysical analysis of these dyes revealed that only 3f and 3m showed aggregation-induced emission behavior in a THF/water mixture (0-99%) with varying water fractions ( fw) leading to bright fluorescence covering the entire visible region, while other derivatives 3g, 3h, and 4e did not show any fluorescence signal. The computational studies of the compounds revealed that the longer wavelength absorption originates from HOMO to LUMO electronic excitation. These dyes exhibited good thermal stability with 5% weight loss temperature in the range of 218-347 °C. The potential application of the donor-acceptor pyranone dyads was demonstrated by fabrication of solution-processed OLEDs. Remarkably, OLED devices prepared using highly emissive compounds 6-(anthracen-9-yl)-4-(methylthio)-2-oxo-2 H-pyran-3-carbonitrile (3m) and 6-(4-methoxyphenyl)-4-(methylthio)-2-oxo-2 H-pyran-3-carbonitrile (3f) displayed pure white emission with CIE coordinates of (0.29, 0.31) and (0.32, 0.32), respectively. Additionally, the resultant devices exhibited external quantum efficiencies of 1.9 and 1.2% at 100 cd m-2, respectively.

First Dual Responsive "Turn-On" and "Ratiometric" AIEgen Probe for Selective Detection of Hydrazine Both in Solution and the Vapour Phase.

A new dual responsive "turn-on" and "ratiometric" aggregation-induced emission luminogen (AIEgen) 3-formyl-5-(piperidin-1-yl)biphenyl-4-carbonitrile 6 a (FPBC 6 a) for selective detection of hydrazine in solution as well as in vapour phase is described. At a low concentration of 2.5 µm, the probe FPBC 6 a is non-fluorescent (turn-off) but remarkably lights up (turn-on with blue emission) in the presence of hydrazine solution (0.25-25 µm). Interestingly, at higher concentrations, the nanoaggregates of FPBC 6 a (>25 µm, 99 % HEPES in DMSO) displayed ratiometric response in the presence of hydrazine with a remarkable hypsochromic shift from the green (500-550 nm) to blue regions (440-480 nm). Furthermore, a real application of FPBC 6 a was successfully demonstrated through the detection and visualization of hydrazine in live cervical cancer cells as well as using portable test strips.

Imaging and Quantitative Detection of Lipid Droplets by Yellow Fluorescent Probes in Liver Sections of Plasmodium Infected Mice and Third Stage Human Cervical Cancer Tissues.

The diagnosis and prognosis of the disease associated with lipid irregularity are areas of extreme significance. In this direction, fluoranthene based yellow fluorescent probes (FLUN-550, FLUN-552, FLUN-547) were designed and synthesized by conjugating the ethanolamine headgroup of the phospholipid phosphatidyl-ethanolamine present in biological membranes. Owing to unique photophysical properties and aqueous compatibility, these probes were successfully employed for staining lipid droplets (LDs) in preadipocytes and Leishmania donovani promastigotes. Furthermore, using the fluorescent probes FLUN-550 and FLUN-552 we successfully imaged and quantitatively detected the excess accumulation of lipids in a liver section of Plasmodium yoelii MDR infected mice (3- to 4-fold) and the tissue sections of third stage human cervical cancer patients (1.5- to 2-fold) compared to normal tissues. To the best of our knowledge, this is the first report of yellow fluorescent probes for imaging and quantitative detection of LDs in human cervical cancer tissues. These new yellow fluorescent lipid probes (FLUN-550 and FLUN-552) showed great potential for diagnosis of cervical cancer patients.

Biocompatible fluorescent carbon quantum dots prepared from beetroot extract for in vivo live imaging in C. elegans and BALB/c mice.

Luminescent carbon quantum dots (CQDs) prepared from aqueous beetroot extract were developed as unique fluorescent nanomaterials for in vivo live animal imaging applications. Blue (B) and green (G) emitting environmentally benign CQDs (particle size of 5 nm and 8 nm, respectively) exhibited bright fluorescence in aqueous medium and were found to be biocompatible, photostable and non-toxic in animal models. The in vivo imaging and toxicity evaluation of both CQDs were performed for the first time in the Caenorhabditis elegans (C. elegans) model, which revealed consistent fluorescence in the gut tissues of the worms without exerting any sign of toxic effects on the nematodes. The in vivo bio-distribution of G-CQDs given by tail vein injection in live BALB/c mice showed optical signals in the lower abdominal regions, mainly in the intestine, and cleared from the body through faeces. The tremendous potential shown by these eco-friendly CQDs in the C. elegans and mice models advocates new hopes for greener CQD nanomaterials as diagnostic tools in the biomedical field.