Antimicrobial evaluation of thiadiazino and thiazolo quinoxaline hybrids as potential DNA gyrase inhibitors; design, synthesis, characterization and morphological studies

To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.

Pure ZnO and Neodymium (Nd) doped ZnO nanoparticles (NPs) were synthesized by the co-precipitation method. The synthesized nanoparticles retained the wurtzite hexagonal structure. From FESEM studies, ZnO and Nd doped ZnO NPs showed nanorod and nanoflower like morphology respectively. The FT-IR spectra confirmed the Zn-O stretching bands at 422 and 451 cm−1 for ZnO and Nd doped ZnO NPs respectively. From the UV-VIS spectroscopic measurement, the excitonic peaks were found around 373 nm and 380 nm for the respective samples. The photoluminescence measurements revealed that the broad emission was composed of ten different bands due to zinc vacancies, oxygen vacancies and surface defects. The antibacterial studies performed against extended spectrum β-lactamases (ESBLs) producing strains of Escherichia coli and Klebsiella pneumoniae showed that the Nd doped ZnO NPs possessed a greater antibacterial effect than the pure ZnO NPs. From confocal laser scanning microscopic (CLSM) analysis, the apoptotic nature of the cells was confirmed by the cell shrinkage, disorganization of cell wall and cell membrane and dead cell of the bacteria. SEM analysis revealed the existence of bacterial loss of viability due to an impairment of cell membrane integrity, which was highly consistent with the damage of cell walls.

The major compounds isolated from the methanolic extract of the aerial parts of Urtica dioica L. were determined as quercetin-3-O-rutinoside (1). kaempherol-3-O-rutinoside (2). and isorhamnetin-3-O-glucoside (3). by chromatographic, chemical (acidic hydrolysis) and spectral (UV, IR, (1)H-NMR, (13)C-NMR) methods. Their immunomodulatory activities were studied in vitro by chemotaxis (Boyden Migration Chamber) and intracellular killing activity (NBT reduction) tests. Compounds 1, 2, 3 and the total flavonoid fraction were determined to have significant chemotactic effects in 4, 8, 16 microg doses. According to the results of the NBT reduction test, all flavonoid glycosides showed high intracellular killing activity. The results of both assays confirmed the immunostimulatory activity of the flavonoid fraction and the isolated flavonoid glycosides on neutrophils suggesting that they could possibly be useful for treating patients suffering from neutrophil function deficiency and chronic granulomatous diseases. Copyright -Copyright 2003 John Wiley & Sons, Ltd