oxadiazoles and Hemolysis

Ultrasound- and microwave-assisted green synthetic strategies were applied to furnish benzofuran-oxadiazole

Topics: A549 Cells; Antineoplastic Agents; Benzofurans; Cell Survival; Chemistry Techniques, Synthetic; Hemolysis; Humans; Microwaves; Molecular Docking Simulation; Neoplasms; Oxadiazoles; Triazoles

A novel series of 5-(3-Chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives was efficiently synthesized and screened for antibacterial, hemolytic and thrombolytic activities. The molecule 7c remained the best inhibitor of all selected bacterial strains and furthermore possessed very low toxicity, 8.52±0.31. Compound 7a 7b and 7f showed very good thrombolytic activity relative to Streptokinase employed as reference drug. In addition to low toxicity and moderately good thrombolytic activity, the synthesized compounds possessed excellent to moderate antibacterial activity, relative to ciprofloxacin. All compounds especially 7b and 7f can be consider for further clinical studies and might be helpful in synthesis of new drugs for treatment of cardiovascular diseases.

Topics: Anti-Bacterial Agents; Bacteria; Ciprofloxacin; Fibrinolytic Agents; Hemolysis; Microbial Sensitivity Tests; Oxadiazoles

Enterococcus faecium is an important nosocomial pathogen. It has a high propensity for horizontal gene transfer, which has resulted in the emergence of MDR strains that are difficult to treat. The most notorious of these, vancomycin-resistant E. faecium, are usually treated with linezolid or daptomycin. Resistance has, however, been reported, meaning that new therapeutics are urgently needed. The 1,2,4-oxadiazoles are a recently discovered family of antimicrobials that are active against Gram-positive pathogens and therefore have therapeutic potential for treating E. faecium. However, only limited data are available on the activity of these antimicrobials against E. faecium.. To determine whether the 1,2,4-oxadiazole antimicrobials are active against MDR and daptomycin-non-susceptible E. faecium.. The activity of the 1,2,4-oxadiazole antimicrobials against vancomycin-susceptible, vancomycin-resistant and daptomycin-non-susceptible E. faecium was determined using susceptibility testing, time-kill assays and synergy assays. Toxicity was also evaluated against human cells by XTT and haemolysis assays.. The 1,2,4-oxadiazoles are active against a range of MDR E. faecium, including isolates that display non-susceptibility to vancomycin and daptomycin. This class of antimicrobial displays rapid bactericidal activity and demonstrates superior killing of E. faecium compared with daptomycin. Finally, the 1,2,4-oxadiazoles act synergistically with daptomycin against E. faecium, with subinhibitory concentrations reducing the MIC of daptomycin for non-susceptible isolates to a level below the clinical breakpoint.. The 1,2,4-oxadiazoles are active against MDR and daptomycin-non-susceptible E. faecium and hold great promise as future therapeutics for treating infections caused by these difficult-to-treat isolates.

Topics: Anti-Bacterial Agents; Daptomycin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Enterococcus faecalis; Enterococcus faecium; Erythrocytes; Gram-Positive Bacterial Infections; Hemolysis; Humans; Kinetics; Microbial Sensitivity Tests; Oxadiazoles; Staphylococcus aureus; Vancomycin; Vancomycin-Resistant Enterococci

Current study is based on the sequential conversion of indolyl butanoic acid (1) into ethyl indolyl butanoate (2), indolyl butanohydrazide (3), and 1,3,4-oxadiazole-2-thiol analogs (4) by adopting chemical transformations. In a parallel series of reactions, 2-bromo-N-phenyl/arylacetamides (7a-l) were synthesized by reacting different amines derivatives (5a-l) with 2-bromoacetyl bromide (6) to serve as electrophile. Then, the synthesized electrophiles (7a-l) were treated with nucleophilic 1,3,4-oxadiazole-2-thiol analog (4) to afford a range of N-substituted derivatives (8a-l). The structural confirmation of all the synthetic compounds was carried out by IR,

Topics: Acetamides; alpha-Glucosidases; Animals; Catalytic Domain; Cattle; Glycoside Hydrolase Inhibitors; Hemolysis; Hypoglycemic Agents; Indoles; Molecular Docking Simulation; Molecular Structure; Oxadiazoles; Structure-Activity Relationship

Secretory phospholipase A

Topics: Animals; Enzyme Inhibitors; Fenoprofen; Group II Phospholipases A2; Hemolysis; Ibuprofen; Male; Mice; Molecular Docking Simulation; Oxadiazoles; Protein Structure, Secondary

A new series of N-substituted derivatives of 2-{(5-phenyl-1,3,4-Oxadiazol-2-yl)sulfanyl}acetamides was synthesized. The synthesis was carried out by converting benzoic acid (1) into ethyl benzoate (2), benzohydrazide (3) and then 5-pheny-1,3,4-Oxadiazol-2-thiol (4) step by st0ep. The target compounds 6a-p were synthesized by reaction of compound 4 with equimolar ratios of different N-alkyl/aryl substituted 2-bromoacetamide (5a-p) in the presence of DMF and sodium hydride (NaH). The spectral (EI-MS, IR, (1)H-NMR) characterization of all the synthesized compounds reveal their successful synthesis. The compounds were also screened for antimicrobial & hemolytic activity and most of them were found to be active against the selected microbial species at variable extent relative to reference standards. But 6h was the most active against the selected panel of microbes. This series showed less toxicity and may be considered for further biological screening and application trial except 6m, possessing higher cytotoxicity.

Topics: Acetamides; Anti-Infective Agents; Disk Diffusion Antimicrobial Tests; Dose-Response Relationship, Drug; Drug Design; Hemolysis; Hemolytic Agents; Humans; Mass Spectrometry; Molecular Structure; Oxadiazoles; Proton Magnetic Resonance Spectroscopy; Spectrophotometry, Infrared; Structure-Activity Relationship

Influenza virus fusion is mediated by its fusion protein, hemagglutinin (HA). HA undergoes a low pH dependent conformational change that results in insertion into the cell membrane bilayer, formation of a fusion pore, and merging of membrane lipids and establishment of cytoplasmic continuity. Erythrocytes, which can serve as targets of influenza virus fusion, display an asymmetric transbilayer arrangement of their phospholipids. The effect of influenza virus fusion on erythrocyte phosphatidylserine asymmetry was determined. Influenza virus were bound to erythrocytes containing the fluorescent membrane probe NBD-PS in the inner leaflet. Induction of fusion by exposure to a low pH environment resulted in movement of PS to the outer leaflet of the cell as well as hemolysis. Insertion of the fusion protein into erythrocytes and subsequent fusion can be distinguished from hemolysis by examining the interaction of a soluble form of HA (BHA) with cells and by monitoring viral fusion at low temperatures. No hemolysis was observed under either condition. BHA binding and insertion into cells did not affect the asymmetry of PS. Incubation of influenza virus fusion at pH 5, 0 degrees C resulted in complete fusion but no outward movement of PS was observed. These findings suggest the viral fusion pore does not involve a rearrangement of the transbilayer phospholipid organization of the target membrane.

Topics: 3T3 Cells; 4-Chloro-7-nitrobenzofurazan; Animals; Erythrocyte Membrane; Fluorescence; Hemagglutinin Glycoproteins, Influenza Virus; Hemagglutinins, Viral; Hemolysis; Humans; Hydrogen-Ion Concentration; Kinetics; Lipid Bilayers; Membrane Fusion; Membrane Lipids; Mice; Orthomyxoviridae; Oxadiazoles; Phosphatidylserines; Taurine; Temperature

The relation between Mycoplasma pulmonis-mediated hemolysis and translocation of a unique fluorescent cholesterol probe was examined. The probe, cholesteryl 12(4-methyl-7-nitrobenz-2-oxa-1,3-diazole) dodecanoate, had fluorescent properties, which permitted microscopic assessment of probe transfer. Significant translocation occurred only after trypsin treatment of the erythrocyte, and the rate of transfer was increased in the presence of bovine serum albumin. This correlated with the previously reported hemolytic activity of M. pulmonis, thus relating the two activities and permitting their integration into a mycoplasma-eukaryotic cell-cell interaction model.

Topics: 4-Chloro-7-nitrobenzofurazan; Cholesterol; Erythrocyte Membrane; Fluorescent Dyes; Hemolysis; Humans; Membrane Lipids; Models, Biological; Mycoplasma; Oxadiazoles; Serum Albumin, Bovine; Trypsin