A new exploration toward adamantane derivatives as potential anti-MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors.

Developing novel antimicrobial agents has become a necessitate due to the increasing rate of microbial resistance to antibiotics. All the newly adamantane derivatives were evaluated for their antimicrobial activities against six MDR clinical pathogenic isolates. The results exhibited that 13 compounds have from potent to good activity. Among those, five derivatives (6, 7, 9, 14a, and 14b) displayed the potent activities against the different isolates tested (MIC < 0.25 µg/ml with bacteria and <8 µg/ml with fungi) compared with Ciprofloxacin (CIP) and Fluconazole (FCA). Additionally, the potent adamantanes showed bactericidal and fungicidal effects based on (MBCs and MFCs) and the time-kill assay. The most active adamantane derivatives 7 and 14b exhibited a synergistic effect of ΣFIC ≤ 0.5 with CIP and FCA against the bacterial and fungal isolates. Moreover, no antagonistic effect appeared for the tested derivatives. Additionally, the interaction of DNA gyrase and topoisomerase IV enzymes with the compounds 6, 7, 9, 14a, and 14b exhibited potent antimicrobial activity using in vitro biochemical assays and gel-based DNA-supercoiling inhibition method. The activity of DNA gyrase and topoisomerase IV enzymes showed inhibitory activity (IC50 ) of 6.20 µM and 9.40 µM with compound 7 and 10.14 µM and 13.28 µM with compound 14b, respectively. Surprisingly, exposing compound 7 to gamma irradiation sterilized and increased its activity. Finally, the in-silico analysis predicted that the most active derivatives had good drug-likeness and safe properties. Besides, molecular docking and quantum chemical studies revealed several important interactions inside the active sites and showed the structural features necessary for activity.

Effect of nanoclay concentration level on the electrical properties of polypropylene under electron irradiation in a SEM.

For studying the electrical properties (charge trapping, transport and secondary electron emission) of the polypropylene-based nanocomposites with different contents of natural clay, the specimens were submitted to electron irradiation of a scanning electron microscope. A device, suitably mounted on the sample holder of the scanning electron microscope, was used to measure two currents (i.e. leakage and displacement currents) induced in the polypropylene-based nanocomposites (polymer nanocomposites) under electron irradiation. The evolution of trapped charge during irradiation for each type of studied polymer nanocomposites is deduced. The amount of trapped charge at the steady state is also determined by measuring the change of secondary electron image size associated to the electron trajectory simulation. It is found, surprisingly, that not only the leakage current increases as a function of clay loading level but also trapped charge. However, this could be related to the increase of conductivity in one hand and to proliferation of interfaces between nanoparticles and neighbouring materials on the other hand. These two processes play crucial role in controlling the carrier transport (through polymer nanocomposites or/and along its surface) closely related to the charge storage and leakage current. Additional experiment using dielectric spectroscopy were performed to show the effect of clay concentration in changing the dielectric relaxation behaviour and to evidence the existence of interfaces between nanoparticles and polymer. The secondary electron emission during electron irradiation is also studied through the total electron yield that is deduced by correlating the measured leakage and displacement currents.

Study of temperature effects on the electrical behavior of polypropylene-clay nanocomposites submitted to electron beam irradiation in a SEM.

Charge transport and electron emission properties in polypropylene and its nanocomposites filled with nanoclay particles submitted to an electron irradiation, in a Scanning Electron Microscope (SEM), are investigated using induced displacement and leakage currents. The measurements have been performed at various temperatures ranging from 20°C to 75°C at a primary beam energy of 20keV and a primary beam current of 1nA with the aim to highlight the effect of temperature and nanoclay content on these properties. The results show, at a given temperature, that the incorporation of clay in polypropylene (PP) matrix paradoxically leads to a concomitant increase in the electrical conductivity and the charge accumulated. In contrast, if the clay content is fixed, there is an increase in conductivity and a reduction of the charge accumulated when the temperature increases. The mobility of charge carriers and the corresponding activation energy are deduced from the measured leakage current during discharging step. The mobility was found to be an order of magnitude higher for the nanocomposites. The study of the influence of the temperature and nanoclay concentration on electron emission yield is also addressed.