Red-sea dolomite as a sustainable catalyst in the synthesis of bis-indolyl methanes with molecular docking validation as HIV-1 replication inhibitor

ABSTRACT. Dolomite minerals were collected from the Red Sea Mountains around the Sokhna region. The rock was collected, rinsed, and crushed using a ball mailing machine and used without further purification. The dolomite sample was characterized using FTIR, XRD, SEM/EDAX, and mapping to ensure their composition and homogeneity. The obtained data reveal that the presence of a homogenous crystalline structure of CaMg(CO3)2. The characterized rock was used as a catalyst in the eco-friendly synthesis of bis-indolyl methane derivatives by reacting two moles of unsubstituted indole and various aromatic aldehydes in the presence of Red-Sea Dolomite mineral as an economical, recyclable, easily obtained, and nontoxic catalyst under solvent-free conditions. The molecular docking study explained that the bis-indolyl methane can be considered as a small molecule stimulator of HIV-1 frameshifting and inhibitor of viral replication.                     KEY WORDS: Indole, Dolomite, HIV-1, Catalyst, Frameshifting, Viral replication   Bull. Chem. Soc. Ethiop. 2021, 35(3), 647-657. DOI: https://dx.doi.org/10.4314/bcse.v35i3.1

Copper-based glass-ceramic as an efficient catalyst in the synthesis of pyrazolo[1,5-a] pyrimidineunder solvent-free condition with docking validation as Covid-19 main protease (Mpro) inhibitor

Copper-based oxide glass-ceramic was successfully synthesized through the single-step melt annealing technique. Synthesized glass-ceramics was characterized using X-ray diffraction (XRD) and scanning electron microscopy (SEM) supported with energy dispersive X-ray (EDX) and mapping. Pyrazolo[1,5-a]pyrimidines 5a-f were synthesized via the reaction of 5-amino-1H-pyrazole-4-carboxamide (1) with enaminones 2a-f in the presence of synthesized oxide glass-ceramic catalyst powder under solvent-free condition. The molecular docking study demonstrated that the COVID-19 main protease (MPro) inhibitor.                     KEY WORDS: Pyrazolopyrimidine, Enaminones, Copper-based catalysis, Solvent-free, COVID-19   Bull. Chem. Soc. Ethiop. 2021, 35(1), 185-196. DOI: https://dx.doi.org/10.4314/bcse.v35i1.1

Vac-and-fill: A micromoulding technique for fabricating microneedle arrays with vacuum-activated, hands-free mould-filling

We report a simple and reproducible micromoulding technique that dynamically fills microneedle moulds with a liquid formulation, using a plastic syringe, triggered by the application of vacuum (‘vac-and-fill’). As pressure around the syringe drops, air inside the syringe pushes the plunger to uncover an opening in the syringe and fill the microneedle mould without manual intervention, therefore removing inter-operator variability. The technique was validated by monitoring the plunger movement and pressure at which the mould would be filled over 10 vacuum cycles for various liquid formulation of varying viscosity (water, glycerol, 20% polyvinylpyrrolidone (PVP) solution or 40% PVP solution). Additionally, the impact of re-using the disposable syringes on plunger movement, and thus the fill pressure, was investigated using a 20% PVP solution. The fill pressure was consistent at 300–450 mbar. It produced well-formed and mechanically robust PVP, poly(methylvinylether/maleic anhydride) and hydroxyethylcellulose microneedles from liquid formulations. This simple and inexpensive technique of micromoulding eliminated the air entrapment and bubble formation, which prevent reproducible microneedle formation, in the resultant microneedle arrays. It provides a cost-effective alternative to the conventional micromoulding techniques, where the application of vacuum (‘fill-and-vac’) or centrifugation following mould-filling may be unsuitable, ineffective or have poor reproducibility

Modeling and numerical investigation of the performance of gas diffusion electrodes for the electrochemical reduction of carbon dioxide to methanol

In this study, a model was built to investigate the role of Cu2O-/ZnO-based gas diffusion electrodes in enhancing the reduction of carbon dioxide into methanol inside an electrochemical cell. The model was simulated using COMSOL Multiphysics software and validated using experimental results. It showed reasonable agreement with an average error of 6%. The model demonstrated the dependence of the methanol production rate and faradic efficiency on process key variables: current density (j = 5-10 mA cm-2), gas flow rate (Qg/A = 10-20 mL min-1 cm-2), electrolyte flow rate, and CO2 gas feed concentration. The results showed a maximum methanol production rate of 50 -mol m-2 s-1 and faradic efficiency of 56% at -1.38 V vs Ag/AgCl. From the economic point of view, it is recommended to use a gas stream of 90% or slightly lower CO2 concentration and an electrolyte flow rate as low as 2 mL min-1 cm-2.The authors would like to convey special thanks to Prof. Mai Kamal El-Din for her willingness to share her knowledge and expertise that are of significant relevance to this work. J.A. gratefully acknowledges the financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under Ramon y Cajal program (RYC-2015-17080). The authors from ́ the Chemical Engineering Department, Cairo University, gratefully acknowledge the financial support provided by the Science and Technology Development Fund (STDF) of Egypt under project ID #11872. R.M.E.-M. acknowledges the support from the Oil and Green Chemistry research center and the Enhanced Oil Recovery Lab, Suez University, Egypt, and STDF (Science and Technology Development Fund) [Project ID 12395]

Undifferentiated HepaRG cells show reduced sensitivity to the toxic effects of M8OI through a combination of CYP3A7-mediated oxidation and a reduced reliance on mitochondrial function

\ua9 2024 The AuthorsThe methylimidazolium ionic liquid M8OI (1-octyl-3-methylimidazolium chloride, also known as [C8mim]Cl) has been detected in the environment and may represent a hazard trigger for the autoimmune liver disease primary biliary cholangitis, based in part on studies using a rat liver progenitor cell. The effect of M8OI on an equivalent human liver progenitor (undifferentiated HepaRG cells; u-HepaRG) was therefore examined. u-HepaRG cells were less sensitive (>20-fold) to the toxic effects of M8OI. The relative insensitivity of u-HepaRG cells to M8OI was in part, associated with a detoxification by monooxygenation via CYP3A7 followed by further oxidation to a carboxylic acid. Expression of CYP3A7 - in contrast to the related adult hepatic CYP3A4 and CYP3A5 forms - was confirmed in u-HepaRG cells. However, blocking M8OI metabolism with ketoconazole only partly sensitized u-HepaRG cells. Despite similar proliferation rates, u-HepaRG cells consumed around 75% less oxygen than B-13 cells, reflective of reduced dependence on mitochondrial activity (Crabtree effect). Replacing glucose with galactose, resulted in an increase in u-HepaRG cell sensitivity to M8OI, near similar to that seen in B-13 cells. u-HepaRG cells therefore show reduced sensitivity to the toxic effects of M8OI through a combination of metabolic detoxification and their reduced reliance on mitochondrial function

Dietary Supplementation of Moringa Oleifera Leaves and Their Nanoparticles to Rabbit Does Altered the Neonates Performance, Behavioural and Physiological Response to Stress

This study was conducted to investigate the effects of supplementing rabbits does with nano-zinc (NZn), nano-moringa (NMo), or moringa extract (MoE) on their growing rabbits (GR; fed on a moringa diet) behaviour, performance, and weaning stress alleviation. Twenty four does were equally divided into 4 groups; NZn-treated dams, NMo-treated dams, moringa extract MoE-treated dams, and non-treated dams (control; NTD) throughout gestation, lactation, and until the weaning of neonates. Immediately after weaning at about 35 days of age, 48 GR [12 from each treated dam group] were subdivided into 8 equal groups (each 12 GR/gp divided into 2 sub-groups: n = 6 per each); one sub group fed on a basal diet (BD) and the other fed on a 5% Moringa olifera-containing ration (MD) for 4 weeks. Feed intake (FI), body weight, and behavioural changes in the GR were recorded. Blood samples were collected at the termination of the experiment to assess oxidative stress (MDA, GSH), growth indicators (T3, T4), and liver and kidney functions. As a result, MD supplementation significantly (P < 0.01) increased FI compared to BD in the GR from control and NZn-treated dams. In addition, MD supplementation resulted in increased feeding and drinking behaviours frequency and duration, while self-grooming was reduced in both NTD and NZn-treated dams in relation to BD supplemented groups. Moreover, MD significantly decreased oxidative stress in GR from NTD. Also, MD induced a significant (P < 0.01) increase in T3 level and enhanced the liver and kidney functions in GR from all treated dams compared to control. Furthermore, MD supplementation increased the economic efficiency of GR. In conclusion, MD supplementation to GRs or treatment of their dams with the mentioned treatments decreased weaning stress, improved rabbit behaviour, and improved economic efficiency, but no significant improvement in the GRs' performance was observed. However, treatments of dams and their GR with MD resulted in GR inability to cope with weaning stress and induced renal and hepatic damage. Thus, it is recommended to supplement GR with MD after weaning or prenatal treatment of their dams with herbal extract or nano-herbal particles, but a combination of both treatments is not recommended

A model for integrating home-work tour scheduling with time-varying network congestion and marginal utility profiles for home and work activities.

The existing literature on activity-based modeling emphasizes that individuals schedule their activities by keeping the whole-day activity pattern in mind. Several attempts have been made to integrate this with network congestion; however, for explicit explanation of travel behavior of individuals, further improvements are required. The proposed model is a combined model that addresses the scheduling of the home-work tour with time-varied network congestion in a fixed-point problem frame-work. Marginal utility profiles that represent individual time-of-day preferences and satiation effect of the activities are incorporated for the measurement of the utility of activity engagement along with the disutility of travel. Consideration of only time-of-day dependent marginal utility profiles of activities in the utility function does not appropriately integrate activities and travel within the tour. The proof is shown analytically and numerically. This finding contradicts earlier research into integration of morning and evening commutes with network congestion. Additionally, the results of two numerical experiments are presented. In the first experiment, an arbitrary dynamic tolling strategy is assumed, and then a detailed analysis is performed to show variation in the balance of trade-offs involved in the process. The second experiment assesses the sensitivity of the combined model through incorporation of different dynamic traffic loading models. Some meaningful observations are drawn from these experiments and are discussed with the identification of avenues for future research

The toxicity of the methylimidazolium ionic liquids, with a focus on M8OI and hepatic effects

Ionic liquids are a diverse range of charged chemicals with low volatility and often liquids at ambient temperatures. This characteristic has in part lead to them being considered environmentally-friendly replacements for existing volatile solvents. However, methylimidazolium ionic liquids are slow to break down in the environment and a recent study at Newcastle detected 1 octyl 3 methylimidazolium (M8OI) – an 8 carbon variant methylimidazolium ionic liquid - in soils in close proximity to a landfill site. The current M8OI toxicity database in cultured mammalian cells, in experimental animal studies and in model indicators of environmental impact are reviewed. Selected analytical data from the Newcastle study suggest the soils in close proximity to the landfill site, an urban soil lacking overt contamination, had variable levels of M8OI. The potential for M8OI - or a structurally related ionic liquid – to trigger primary biliary cholangitis (PBC), an autoimmune liver disease thought to be triggered by an unknown agent(s) in the environment, is reviewed