Development of Novel 1,3-Disubstituted-2-Thiohydantoin Analogues with Potent Anti-Inflammatory Activity; In Vitro and In Silico Assessments

Inflammation is the main cause of several autoimmune diseases, including type I diabetes, rheumatoid arthritis, bullous pemphigoid, paraneoplastic pemphigoid, and multiple sclerosis. Currently, there is an urgent demand for the discovery of novel anti-inflammatory drugs with potent activity but also safe for long-term application. Toward this aim, the present study reported the design, synthesis, and characterization of a set of novel 1,3-disubstituted-2-thiohydantoins derivatives. The anti-inflammatory activity of synthesized compounds was assessed against murine leukemia cell line (RAW264.7) by evaluating the cytotoxicity activity and their potency to prevent nitric oxide (NO) production. The results revealed that the synthesized compounds possess a considerable cytotoxic activity together with the ability to reduce the NO production in murine leukemia cell line (RAW264.7). Among synthesized compounds, compound 7 exhibited the most potent cytotoxic activity with IC50 of 197.68 μg/mL, compared to celecoxib drug (IC50 value 251.2 μg/mL), and demonstrated a significant ability to diminish the NO production (six-fold reduction). Exploring the mode of action responsible for the anti-inflammatory activity revealed that compound 7 displays a significant and dose-dependent inhibitory effect on the expression of pro-inflammatory cytokines IL-1β. Furthermore, compound 7 demonstrated the ability to significantly reduce the expression of the inflammatory cytokines IL-6 and TNF-α at 50 μg/mL, as compared to Celecoxib. Finally, detailed molecular modelling studies indicated that compound 7 exhibits a substantial binding affinity toward the binding pocket of the cyclooxygenase 2 enzyme. Taken together, our study reveals that 1,3-disubstituted-2-thiohydantoin could be considered as a promising scaffold for the development of potent anti-inflammatory agents.the Faculty of Science, Port Said University and Suez Canal University, EgyptPrincess Nourah bint Abdulrahman University, Riyadh, Saudi Arabiathe Faculty of Medicine, Al-Azhar University, EgyptPeer Reviewe

Efficient adsorption of Rhodamine B using a composite of Fe3O4@zif-8: Synthesis, characterization, modeling analysis, statistical physics and mechanism of interaction

ABSTRACT. The utilization of a metal organic framework (ZIF-8) modified by Fe3O4 nanoparticles was used to accomplish adsorption of Rhodamine B (RB) from aqueous solutions. SEM, XRD, IR, and BET analyses were all used to characterize the composite (Fe3O4@ZIF-8). The surface area of this adsorbent was 478.4 m2/g. X-Ray diffraction spectroscopy was used to detect surface modification utilizing electron microscopy (SEM) scanning with 48 nm in diameter average particle size according to a statistical physics method. Fe3O4@ZIF-8 appears to have dispersive interactions and pore characteristics, according to quantum chemistry simulations. On the adsorption of RB, the influences of contact time, adsorbent quantity, dye concentration, and temperature were studied. The Langmuir and Freundlich adsorption isotherm models were used to study the adsorption isotherms. Anticipated overall adsorption potential was 647.5 mg/g, with a zero-charge point (pHPZC) of 4.3. The adsorption isotherm was fitted using Langmuir whereas pseudo second order was used to match the kinetics. Energy of adsorption (Ea) is 28.7 kJ/mol, indicating a chemisorption phase. The adsorption process is endothermic and unpredictable, according to thermodynamic experiments. It was also looked into using ethanol as a solvent in the desorption of deposited cationic dye.   KEY WORDS: Fe3O4@ZIF-8, Rhodamine B, Adsorption models, Thermodynamics   Bull. Chem. Soc. Ethiop. 2023, 37(1), 211-229.                                                                DOI: https://dx.doi.org/10.4314/bcse.v37i1.17                                                     &nbsp

Minerals and chelated-based manganese fertilization influences the productivity, uptake, and mobilization of manganese in wheat (Triticum aestivum L.) in sandy loam soils

Manganese (Mn) is an essential micronutrient in plants, and it is necessary for hydrolysis in photosystem II, chlorophyll biosynthesis, and also chloroplast breakdown. Limited Mn availability in light soil resulted in interveinal chlorosis, poor root development, and the development of fewer tillers, particularly staple cereals including wheat, while foliar Mn fertilizers were found efficient in improving crop yield as well as Mn use efficiency. In the above context, a study was conducted in consecutive two wheat growing seasons for screening of the most effective and economical Mn treatment for improving the yield and Mn uptake in wheat and to compare the relative effectiveness of MnCO3 against the recommended dose of MnSO4 for wheat. To fulfill the aims of the study, three manganese products, namely, 1) manganese carbonate MnCO3 (26% Mn w/w and 3.3% N w/w), 2) 0.5% MnSO4·H2O (30.5% Mn), and 3) Mn-EDTA solution (12% Mn), were used as experimental treatments. Treatments and their combinations were as follows: two levels of MnCO3 (26% Mn) @ 750 and 1,250 ml ha−1 were applied at the two stages (i.e., 25–30 and 35–40 days after sowing) of wheat, and three sprays each of 0.5% MnSO4 (30.5% Mn) and Mn-EDTA (12% Mn) solution were applied in other plots. The 2-year study showed that Mn application significantly increased the plant height, productive tillers plant−1, and 1,000 grain weight irrespective of fertilizer source. The results of MnSO4 for grain yield wheat as well as uptake of Mn were statistically at par with both levels (750 and 1,250 ml ha−1) of MnCO3 with two sprays at two stages of wheat. However, the application of Mn in the form of 0.5% MnSO4·H2O (30.5% Mn) was found more economical than MnCO3, while the mobilization efficiency index (1.56) was found maximum when Mn was applied in MnCO3 with two sprays (750 and 1,250 ml ha−1) in the two stages of wheat. Thus, the present study revealed that MnCO3 can be used as an alternative to MnSO4 to enhance the yield and Mn uptake of wheat

Rheological and Nutritional Properties and Sensory Evaluation of Bread Fortified with Natural Sources of Calcium

By-products of oyster shell and egg shell are new candidates for use as calcium supplements. The effect of the fortification of bread with natural sources of calcium such as skim milk powder, egg shell powder, and oyster shell powder at levels of 10%, 2%, and 2%, respectively, on the rheological, nutritional, and sensory properties was determined. Compared to the control bread, breads fortified with egg and oyster shells had a higher water absorption (%), dough development time, dough stability, mixing time, heat of transition, and setback viscosity but a lower weakening index. Skim milk-fortified bread had the lowest levels of carbohydrates and energy of the bread formulations tested. Oyster shell-fortified bread showed significantly higher contents of protein, ash, fibre, and carbohydrates. Sensory evaluation revealed that the breads fortified with egg and oyster shells showed lower scores for odour and general acceptability compared with the control bread and the bread fortified with skim milk powder. Higher levels of minerals and amino acids except proline were estimated in the tested breads. These results indicate that the addition of natural sources of calcium to bread could positively impact its technological and nutritional properties

Functional role of selenium-fortified yogurt against aflatoxin-contaminated nuts in rats

Abstract Background Aflaxions are a group of chemically toxic fungal metabolites produced by species of the genus Aspergillus. Nuts can be contaminated by fungi, resulting in the production of mycotoxins. The present study was performed to investigate the ability of selenium-fortified yogurt to counteract the adverse effects of consuming 3% experimental nuts (pistachios, cashews, walnuts, almonds and hazelnuts) contaminated with aflatoxins in experimental rats. First, the total aflatoxins concentrations were estimated in fresh nuts, and in nuts after 6 months of storage, and selenium-fortified yogurt was prepared. Rats were classified into a negative control group (fed a standard diet with a 3% mixture of fresh safe nuts), a positive control group (fed a standard diet with a 3% mixture of nuts contaminated with aflatoxins after storage at 25 °C for 6 months) and treated groups that fed on pistachios with selenium-fortified yogurt, cashews with selenium-fortified yogurt, walnuts with yogurt fortified with selenium, almonds with selenium-fortified yogurt and hazelnuts with selenium-fortified yogurt (fed a standard diet with 3% individual nuts contaminated with aflatoxins and 160 ml/kg body weight of selenium-fortified yogurt daily through a stomach tube). Results The negative effects of aflatoxins on weight gain and food intake were reversed by selenium-fortified yogurt. This yogurt also led to a significant decrease in serum cholesterol, TG, LDLc, VLDLc, total lipids, phospholipids, glucose and atherogenic indexes (CHO/HDLc and LDLc/HDLc) and an increase in serum HDLc, haemoglobin, PCV, liver TG and glycogen at p < 0.05. In addition, the study showed a significant decrease in liver cholesterol and total lipids compared to the positive control rat group, which consumed 3% mixed nuts contaminated with aflatoxins and simultaneously restored these parameters to be close to those in the control group. The results were corroborated by histopathological examination of the liver and kidneys. Conclusions The most prominent conclusion is that selenium-fortified yogurt reduces side effects from consumption of nuts contaminated with aflatoxins. It is recommended to consume functional selenium-fortified yoghurt for its nutritional values and for alleviating the harmful effect of aflatoxins in nuts

Effect of Low-Calorie Pumpkin Jams Fortified with Soybean on Diabetic Rats: Study of Chemical and Sensory Properties

This research investigated the chemical analysis and sensory evaluation of low-calorie formulated pumpkin jams after storage for six months and the effects of the consumption of low-calorie jams on diabetic rats. Pumpkin jam with sucrose, fructose, stevia, and aspartame sweeteners and soybean was prepared and stored at 10°C for six months. Rats were divided into group 1 (negative control), group 2 (positive diabetic groups), and groups 3, 4, and 5 (diabetic groups treated with 10% sucrose, fructose, and stevia soybean jam, respectively). The results indicated that the contents of protein, fat, ash, and fibre were increased in the low-calorie formulated pumpkin jams. The highest sensory scores were recorded for sucrose and fructose soybean jams and then for stevia soybean jam, while the aspartame soybean jam showed significantly lower scores after storage for 3 and 6 months. Rat groups 4 and 5 showed significant decreases in the glucose level, and liver function enzymes activity showed significant increases in insulin and glycogen levels compared to group 2. Conclusion. Low-calorie pumpkin jams with soybean can be stored for 3 months at 10°C without any change. Stevia pumpkin jam with soybean has antidiabetic effects

Charge-transfer interaction of aspartame and neotame with several π-acceptors: Stoichiometric data

This data article is related to a research paper entitled ''Correlations between spectroscopic data for charge-transfer complexes of two artificial sweeteners, aspartame and neotame, generated with several π-acceptors'' [J. Mol. Liq. 333 (2021) 115904] [1]. Herein we present stoichiometric data of charge-transfer (CT) complexes generated from the interaction between aspartame and neotame with three π-acceptors in methanol solvent at room temperature. The investigated π-acceptors were picric acid (PA), chloranilic acid (CA), and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), where the methods used to determine the stoichiometry of the CT interaction were the spectrophotometric titration method and the Job's continuous variation method

Insights into Asparaginase from Endophytic Fungus Lasiodiplodia theobromae: Purification, Characterization and Antileukemic Activity

Endobiotic fungi are considered as a reservoir of numerous active metabolites. Asparaginase is used as an antileukemic drug specially to treat acute lymphoblastic leukaemia. The presented study aims to optimize the media conditions, purify, characterize, and test the antileukemic activity of the asparaginase induced from Lasiodiplodia theobromae. The culture medium was optimized using an experiment designed by The Taguchi model with an activity ranging from 10 to 175 IU/mL. Asparaginase was induced with an activity of 315 IU/mL. Asparaginase was purified with a specific activity of 468.03 U/mg and total activity of 84.4 IU/mL. The purified asparaginase showed an approximate size of 70 kDa. The purified asparaginase showed an optimum temperature of 37 &deg;C and an optimum pH of 6. SDS reduced the activity of asparaginase to 0.65 U/mL while the used ionic surfactants enhanced the enzyme activity up to 151.92 IU/mL. The purified asparaginase showed a Km of 9.37 &micro;M and Vmax of 127.00 &micro;M/mL/min. The purified asparaginase showed an IC50 of 35.2 &plusmn; 0.7 IU/mL with leukemic M-NFS-60 cell lines and CC50 of 79.4 &plusmn; 1.9 IU/mL with the normal WI-38 cell line. The presented study suggests the use of endophytic fungi as a sustainable source for metabolites such as asparaginase, provides an opportunity to develop a facile, eco-friendly, cost-effective, and rapid synthesis of antileukemic drugs, which have the potential to be used as alternative and reliable sources for potent anticancer agents