Rational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors

A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesised based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a methyl group to bring the molecular weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesised compounds in addition to the previously identified hits were subjected to molecular docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimised to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimised ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesised compounds indicate that these compounds possess good pharmacokinetic properties.     

Synthesis,SAR and Unanticipated Pharmacological Profiles of Analogues of the mGluR5 Ago‐potentiator ADX‐47273

An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago‐potentiator ADX‐47273. This effort identified key substituents in the 3‐position of oxadiazole that engendered either mGluR5 ago‐potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9‐fold) of the glutamate CRC reported to date as well as providing improved physiochemical properties.

     

Spectral and spatial dynamics of a multimode GaN-based blue laser diode

ABSTRACT

High-resolution spectral analysis of a multimode GaN-based blue laser diode was performed as a function of temperature and current both below and above the threshold levels. Maps of longitudinal modes evolution as a function of current and temperature were obtained from the highly resolved emission spectra of the laser diode. The evolution of emitted longitudinal modes with current and temperature exhibited redshifts at rates of 0.0059 nm/mA and 0.0149 nm/°C, respectively. Similarly, the laser gain profile was observed to shift towards longer wavelengths but with rates of 0.022 nm/mA and 0.0439 nm/°C. The longitudinal mode spacing of 0.0540 nm was experimentally evaluated and compared with its equivalent theoretically predicted value.     

Effect of Honey as Partial Sugar Substitute on Pasting Properties,Consumer Preference and Shelf Stability of Cassava-Wheat Composite Bread

The effect of partial substitution of sugar with liquid honey on the pasting properties of cooked dough made from cassava-wheat composite (10:90) flour as well as the sensory preference and shelf stability of its bread was investigated. Sucrose (S) in the bread recipe formulation was substituted with honey (H) at levels 0, 10, 20, 30, 40 and 50%, respectively to give 6 treatments, namely 0H:100S, 10H:90S, 20H:80S, 30H:70S, 40H:60S and 50H:50S. Amylograph pasting properties of the dried crumbs were determined using standard analytical procedures. Fresh bread samples were subjected to sensory evaluation and fungal count during storage (6 days). Peak, final and setback viscosities of bread crumb decreased (32.29 to 25.33, 58.54 to 43.00 and 30.96 to 23.66 RVU), respectively as the level of honey inclusion increased. Honey substitution levels used did not significantly (p > 0.05) affect aroma and texture of the bread samples but composite bread with 20% level of honey substitution was most preferred in terms of colour while composite bread with 30% level of honey substitution was most acceptable in terms of taste and overall acceptability. Fungal count in stored honey-cassava-wheat bread varied significantly (p < 0.05) from 0.6 to 4.0 × 10², 1.0 to 6.9 × 10², 2.2 to 57.0 × 10², 32.0 to 135.7 × 10², 34.0 to 140.0 × 10² and 42.0 to 159.3 × 10²) cfu/ml from day 1 to day 6, respectively. From the study, it was concluded that substitution of sugar with honey in dough formulations significantly (p < 0.05) affects dough pasting properties, improves acceptability of the composite bread and reduces staling rate.     

Molecular and phenotypic characterization of Staphylococcus aureus strains isolated from carcass swabs and carcass drips of chickens slaughtered in the informal market in Gauteng Province,South Africa

The study was conducted to characterize Staphylococcus aureus strains from swabs and drips of dressed chicken carcasses sold at outlets in six townships in the informal market in Gauteng province, South Africa, using molecular and phenotypic methods. Seven genes (6 toxins and 1 antimicrobial resistance) comprising staphylococcal enterotoxin A (SEA), B (SEB), C (SEC), D (SED), exfoliative toxin A, toxic shock syndrome toxin, and MecA encoding methicillin resistance were assayed using polymerase chain reaction. The resistance of the S. aureus strains to 18 antimicrobial agents was determined using the disk diffusion method. The frequency of detection of the six toxin genes was sea (52.2%), followed by seb (10.9%), sec (6.5%), sed (2.2%), eta (93.5%), and tst (19.6%). The mecA gene was detected in 4.3% of the isolates. The predominant profiles of toxin genes detected were sea-eta (37.0%). All 63 isolates of S. aureus were resistant to one or more antimicrobial agents. The frequency of resistance was high to spectinomycin (98.4%), nalidixic acid (85.7%), and penicillin (84.1%), but low to gentamycin (1.6%) and cefotaxime (1.6%). The high frequency of toxin genes and antimicrobial resistance gene observed in S. aureus isolates from chicken could pose a challenge to food safety and may have therapeutic and zoonotic implications.     

Movement of water columns in Lake Kainji

Seasonal flooding, the corresponding variations in the flow regime and the attendant influx of organic and inorganic materials into Lake Kainji are producing environmental changes in the lake system. The physical size of the lake, however, makes it impossible for field crews to carry out badly needed regular synoptic surveys of the lake. Earlier studies have suggested a link between horizontal turbidity gradients and general pattern of circulation in the lake. In this study, ratioing of the spectral albedo in selected multi-seasonal and multi-spectral scanner (MSS) bands of LANDSAT satellite have shown a significant correlation with the turbidity characteristics of the lake monitored between 1972 and 1974. The spectral classification of the lake's water, using remote sensing technique, has been found useful in charting the movement of different water masses within the lake.     

Effect of sensitization heat treatment on properties of Al–Mg alloy AA5083-H116

Al–Mg alloy AA5083 is a sheet and plate alloy used mainly for marine application as well as for structural components in transportation and military applications. The strength is derived from solid solution strengthening and strain hardening. The properties of as-received and sensitized samples of AA5083-H116 were investigated using microhardness measurements, tensile testing, optical microscopy, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS), and Nitric Acid Mass Loss Test (NAMLT). The results show that both chemical and mechanical properties of the alloy decreased with increasing sensitization temperature and time. The deterioration in chemical property, which was measured in terms of the level of susceptibility to Intergranular Corrosion (IGC), is attributed to grain boundary precipitation of magnesium-rich particles. The loss in tensile and hardness properties is attributed to softening caused partly by decrease in Mg solute solid solution concentration with increasing sensitization time and temperature and partly by recrystallization at elevated temperatures.     

Electrodeposition of fluorine-doped cadmium telluride for application in photovoltaic device fabrication

Electrodeposition (ED) technique has been used to deposit thin-film cadmium telluride (CdTe) on glass-/fluorine-doped tin oxide substrates using a two-electrode system from acidic, aqueous medium containing Cd(NO₃)₂ 4H₂O, TeO₂ and CdF₂ as dopants. Photoelectrochemical cell measurement, DC conductivity measurement, X-ray diffraction, optical absorption, thickness measurement and atomic force microscopy were carried out to study the electrical, structural, optical, compositional and morphological properties of the as-grown, heat-treated and CdCl₂-treated ED-CdTe layers, respectively. The characterization data obtained signified 1370 mV as the best growth potential and CdCl₂ treatment at 400 °C for 15 min as the best post-growth treatment to achieve an optimal result.