Development of Antibacterial,Degradable and pH-Responsive Chitosan/Guar Gum/Polyvinyl Alcohol Blended Hydrogels for Wound Dressing

The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels’ crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker–Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R² = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.     

Computational Approaches for the Design of Novel Anticancer Compounds Based on Pyrazolo[3,4-d]pyrimidine Derivatives as TRAP1 Inhibitor

In the present in-silico study, various computational techniques were applied to determine potent compounds against TRAP1 kinase. The pharmacophore hypothesis DHHRR_1 consists of important features required for activity. The 3D QSAR study showed a statistically significant model with R² = 0.96 and Q² = 0.57. Leave one out (LOO) cross-validation (R² CV = 0.58) was used to validate the QSAR model. The molecular docking study showed maximum XP docking scores (−11.265, −10.532, −10.422, −10.827, −10.753 kcal/mol) for potent pyrazole analogs (42, 46, 49, 56, 43), respectively, with significant interactions with amino acid residues (ASP 594, CYS 532, PHE 583, SER 536) against TRAP1 kinase receptors (PDB ID: 5Y3N). Furthermore, the docking results were validated using the 100 ns MD simulations performed for the selected five docked complexes. The selected inhibitors showed relatively higher binding affinities than the TRAP1 inhibitor molecules present in the literature. The ZINC database was used for a virtual screening study that screened ZINC05297837, ZINC05434822, and ZINC72286418, which showed similar binding interactions to those shown by potent ligands. Absorption, distribution, metabolism, and excretion (ADME) analysis showed noticeable results. The results of the study may be helpful for the further development of potent TRAP1 inhibitors     

Sage,Salvia officinalis L., Constituents,Hepatoprotective Activity,and Cytotoxicity Evaluations of the Essential Oils Obtained from Fresh and Differently Timed Dried Herbs: A Comparative Analysis

Sage, Salvia officinalis L., is used worldwide as an aromatic herb for culinary purposes as well as a traditional medicinal agent for various ailments. Current investigations exhibited the effects of extended dryings of the herb on the yields, composition, oil quality, and hepatoprotective as well as anti-cancer biological activities of the hydrodistillation-obtained essential oils from the aerial parts of the plant. The essential oils’ yields, compositions, and biological activities levels of the fresh and differently timed and room-temperature dried herbs differed significantly. The lowest yields of the essential oil were obtained from the fresh herbs (FH, 631 mg, 0.16%), while the highest yield was obtained from the two-week dried herbs (2WDH, 1102 mg, 0.28%). A notable decrease in monoterpenes, with increment in the sesquiterpene constituents, was observed for the FH-based essential oil as compared to all the other batches of the essential oils obtained from the different-timed dried herbs. Additionally, characteristic chemotypic constituents of sage, i.e., α-pinene, camphene, β-pinene, myrcene, 1, 8-cineole, α-thujone, and camphor, were present in significantly higher proportions in all the dried herbs’ essential oils as compared to the FH-based essential oil. The in vivo hepatoprotective activity demonstrated significant reductions in the levels of AST, ALT, and ALP, as well as a significant increase in the total protein (p < 0.05) contents level, as compared to the acetaminophen (AAP) administered experimental group of rats. A significant reduction (p < 0.05) in the ALT level was demonstrated by the 4WDH-based essential oil in comparison to the FH-based essential oil. The levels of creatinine, cholesterol, and triglycerides were reduced (p < 0.05) in the pre-treated rats by the essential oil batches, with non-significant differences found among them as a result of the herbs dryings based oils. A notable increase in the viability of the cells, and total antioxidant capacity (TAOxC) levels, together with the reduction in malondialdehyde (MDA) levels were observed by the essential oils obtained from all the batches as compared with the AAP-treated cell-lines, HepG-2, HeLa, and MCF-7, that indicated the in vitro hepatoprotective effects of the sage essential oils. However, significant improvements in the in vivo and in vitro hepatoprotective activities with the 4WDH-based oil, as compared to all other essential oil-batches and silymarin standard demonstrated the beneficial effects of the drying protocol for the herb for its medicinal purposes.     

Predicting Homoclinic Bifurcations in Planar Autonomous Systems

An analytical method to predict the homoclinic bifurcation in a planar autonomous self-excited weakly nonlinear oscillator is presented. The method is mainly based on the collision between the periodic orbit undergoing the homoclinic bifurcation and the saddle fixed point. To illustrate the analytical predictive criteria, two typical examples are investigated. The results obtained in this work are then compared to Melnikov's technique and to a previous criterion based on the vanishing of the frequency. Numerical simulations are also provided.     

The electrochemical behaviour of polycrystalline silver electrodes in Na2CO3 solution and the effect of ClO− 4 ions

The electrochemical behaviour of polycrystalline silver electrodes in Na₂CO₃ solutions was studied under potentiodynamic and potentiostatic conditions and complemented with X-ray diffraction analysis. Potentiodynamic E/i anodic curves exhibit active passive transition prior to an oxygen evolution reaction. The active region involves a small peak AI followed by a major peak AII before the passive region. Peak AI is assigned to the formation of an Ag₂O layer while peak AII is due to the formation of an Ag₂CO₃ layer. The height of the anodic peaks increases with increasing Na₂CO₃ concentration, scan rate and temperature. The effect of increasing additions of NaClO₄ on the electrochemical behaviour of Ag in Na₂CO₃ solutions was investigated. The perchlorate ions stimulate the active dissolution of Ag, presumably as a result of the formation of soluble AgClO₄ salt. In the passive region, ClO⁻ ₄ ions tend to break down the dual passive film, leading to pitting corrosion at a certain critical pitting potential. The pitting potential decreases with ClO⁻ ₄ concentration. Potentiostatic current/time transients showed that the formation of Ag₂O and Ag₂CO₃ layers involves a nucleation and growth mechanism under diffusion control. However, in the presence of ClO⁻ ₄ ions, the incubation time for pit initiation decreases on increasing the anodic potential step. Received: 3 July 1998 / Accepted: 10 March 1999     

Synthesis of 4‐amino‐3‐cyano‐2‐ methylsulfanyl‐1H‐[1,5]benzodiazepine,benzo[1,3]azole,and pyrazolobenzo[1,3]azole derivatives via a new utility of bis(methylsulfanyl)methylene derivatives

Novel polysubstituted 1,5‐benzodiazepine 5 , 2,2‐bis(methylthio)benzoxazoles 8a–d , 2,2‐bis‐ (acetyl)benzoxazole 8e , 2‐(3‐methyl‐1‐phenylpyrazolo‐ 4‐yl)benzoazole derivatives 16a–c , as well as the previously reported 2‐di[cyano(acetyl)‐methylene]benzothiazoles 7a,b have been obtained via a new utility of ketene dithioacetals 1a,b and 12 with aniline derivatives 2 . Rationales for the reactions pathways are presented. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:407–412, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20031     

Switching Chirophilic Self-assembly: From meso-structures to Conglomerates in Liquid and Liquid Crystalline Network Phases of Achiral Polycatenar Compounds

Spontaneous generation of chirality from achiral molecules is a contemporary research topic with numerous implications for technological applications and for the understanding of the development of homogeneous chirality in biosystems. Herein, a series of azobenzene based rod-like molecules with an 3,4,5-trialkylated end and a single n-alkyl chain involving 5 to 20 aliphatic carbons at the opposite end is reported. Depending on the chain length and temperature these achiral molecules self-assemble into a series of liquid and liquid crystalline (LC) helical network phases. A chiral isotropic liquid (Iso₁^[*^]) and a cubic triple network phase with chiral I23 lattice were found for the short chain compounds, whereas non-cubic and achiral cubic phases dominate for the long chain compounds. Among them a mesoscale conglomerate with I23 lattice, a tetragonal phase (Tet_bi) containing one chirality synchronized and one non-synchronized achiral network, an achiral double network meso-structure with Ia d space group and an achiral percolated isotropic liquid mesophase (Iso₁) were found. This sequence is attributed to an increasing strength of chirality synchronization between the networks, combined with a change of the preferred mode of chirophilic self-assembly between the networks, switching from enantiophilic to enantiophobic with decreasing chain length and lowering temperature. These nanostructured and mirror symmetry broken LC phases exist over wide temperature ranges which is of interest for potential applications in chiral and photosensitive functional materials derived from achiral compounds.     

Synthesis of hindered hydrazones and their reaction with thionyl chloride

Hydrazones 12a–c and ketazines 13a–c were prepared by the reaction of ketones 11a–c with hydrazine hydrate depending on the temperature and the reaction time. Some ketone (aryl)hydrazone derivatives 14a,c,e reacted with thionyl chloride to afford the chlorothiadiazoline derivatives 15a–c . Surprisingly, the chlorine atom in the latter compounds was found to undergo smooth nucleophilic substitution, and by boiling these compounds in absolute ethanol gave the corresponding ethoxythiadiazoline derivatives 16a–c . The structure of the ethoxythiadiazoline 16b was confirmed by single crystal X‐ray determination. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:223–228, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10125     

Naturally Available Flavonoid Aglycones as Potential Antiviral Drug Candidates against SARS-CoV-2

Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of Anastatica hierochuntica L., Citrus reticulata Blanco, and Kickxia aegyptiaca (L.) Nabelek. They were identified as taxifolin (1), pectolinarigenin (2), tangeretin (3), gardenin B (4), and hispidulin (5). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (KI), IC₅₀ = 66.72 µg/mL) as a reference standard. Moreover, in vitro screening against SARS-CoV-2 was evaluated. Compounds 2 and 3 showed the highest virus inhibition with IC₅₀ 12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced in vitro and in vivo studies of the examined isolated flavonoids, especially pectolinarigenin (2), tangeretin (3), and gardenin B (4), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.     

Fruit Wastes as a Valuable Source of Value-Added Compounds: A Collaborative Perspective

The by-products/wastes from agro-food and in particular the fruit industry represents from one side an issue since they cannot be disposed as such for their impact on the environment but they need to be treated as a waste. However, on the other side, they are a source of bioactive healthy useful compounds which can be recovered and be the starting material for other products in the view of sustainability and a circular economy addressing the global goal of “zero waste” in the environment. An updated view of the state of art of the research on fruit wastes is here given under this perspective. The topic is defined as follows: (i) literature quantitative analysis of fruit waste/by-products, with particular regards to linkage with health; (ii) an updated view of conventional and innovative extraction procedures; (iii) high-value added compounds obtained from fruit waste and associated biological properties; (iv) fruit wastes presence and relevance in updated databases. Nowadays, the investigation of the main components and related bioactivities of fruit wastes is being continuously explored throughout integrated and multidisciplinary approaches towards the exploitation of emerging fields of application which may allow to create economic, environmental, and social value in the design of an eco-friendly approach of the fruit wastes.