Introduction: Modern drug discovery increasingly relies on the concept of hybrid molecules—structures that combine two or more pharmacophoric elements into a single scaffold. This approach allows for the fine-tuning of pharmacological properties and may offer improved selectivity, efficacy, and safety. In this context, anthranilic acid stands out as a versatile building block, already known for its spectrum of biological activities.

Aim: This study aimed to design and synthesize novel anthranilic acid-based hybrid molecules with improved pharmacokinetic and pharmacodynamic properties.

Methods: A combination of cheminformatics tools (SwissADME, PASS, ProTox-II) was used to guide the design of a focused library of target compounds. The synthetic routes involved amide bond formation between anthranilic acid derivatives and substituted 2-phenylethylamines. All compounds were purified and characterized using standard spectroscopic techniques, including NMR, IR, and HRMS. Computational drug-likeness parameters, such as Lipinski compliance, topological polar surface area, and predicted toxicity classes, were evaluated to support candidate selection.

Results: The resulting hybrid structures integrate multiple pharmacophores and demonstrate favorable predicted ADME/tox properties. The synthetic procedures were efficient and reproducible, yielding structurally confirmed compounds ready for further biological exploration.

Conclusion: The generated hybrid structures show promising in silico drug-likeness and synthetic accessibility. This work provides a strong foundation for developing new small molecules aimed at treating disorders involving smooth muscle dysfunction and inflammation.

Acknowledgments: This study is supported by the Bulgarian Ministry of Education, National Program “Young Scientists and Postdoctoral Students–2”, Project № MUPD-HF-017.

Introduction: It is generally known that Thiadiazole derivatives, particularly those that inhibit Aldose reductase, Alpha amylase, Monoglycerol lipase and Glucagon like Peptide- 1, are strong antidiabetic agents. Glybuzole, Pioglitazone and other similar products are among the marketed goods.

Objective: In order to investigate the possibility of these compounds serving as multi-targeted enzyme receptor inhibitors. The molecules showcased in the current study were designed and synthesized as thiadiazole derivatives and further evaluated for in-silico Antidiabetic Activity.

Methods: The titled compounds as hybrid derivatives were prepared in two steps. First step involved synthesis of substituted thiadiazole intermediates using thiosemicarbazide. In second step, the final compounds were synthesisd using various substituted thiadiazoles and isatin in presence of ethanol and glacial acetic acid.

Results: The docking study was conducted for six synthesized compounds (2a-2f) and PDB Ids were procured and used as anti-diabetic targets 1US0 (aldose reductase), 4W93 (alpha amylase), 5UZN (monoglycerol lipase),and 3IOL (glycogen like protein), considering binding affinity, Lipinski's rule, and ADME properties through computational methods. All compounds passed the initial in silico screening. Among them, compounds 2a and 2b met Lipinski's criteria. Compound 2a showed the strongest binding affinity -10.6, -9.8, and -7.4, while 2b followed with -10.2, -9.4, -7.5 and -7.0. These results suggest that compounds 2a and 2b are promising candidates for further pre-clinical and in-vitro studies.

References:

1. Dhruzhinina, T.V.; Kondrashova, N.N.; Shvekhgeimer, M.G.A.; Synthesis of new derivatives of polycapromide graft copolymers containing 2‐(4‐Aminophenyl)Quinoline‐4‐carboxylic acid fragments. Fibre Chemistry. 36, 2004, 8‐11.

Honey is widely recognised not only for its nutritional and therapeutic properties but also as a natural bioindicator of environmental pollution due to its botanical and geographical origin. In this preliminary study, we assessed the presence of toxic elements in fourteen unifloral and multifloral honeys collected from different regions of northern Algeria, with the aim of evaluating potential public health risks and levels of environmental contamination. The concentrations of selected heavy metals—copper (Cu), iron (Fe), zinc (Zn), cadmium (Cd), and lead (Pb)—were determined using atomic absorption spectrometry (AAS) or inductively coupled plasma mass spectrometry (ICP-MS), depending on the element. Statistical analyses were conducted to explore regional variability and identify potential sources of contamination. The results revealed a wide range of concentrations, namely Cu (0.133–1.975 µg/kg), Fe (1.11–28.04 mg/kg), Zn (4.40–26.30 mg/kg), Cd (1.119–39.521 µg/kg), and Pb (11.515–77.216 µg/kg). Several samples exceeded internationally recommended safety limits for levels of heavy metals such as Cd and Pb, raising concerns regarding long-term dietary exposure. Significant geographical differences were observed, suggesting the influence of local environmental factors and anthropogenic activities. These findings highlight the importance of routine heavy metal monitoring in honey and support its application in environmental surveillance and food safety risk management.

The increasing demand for natural compounds with functional properties in the food, pharmaceutical, and cosmetic industries highlights the importance of sustainable sourcing. Beetroot, rich in betalains, with significant antioxidant potential, is a prime candidate for valorization, especially considering the considerable waste generated during its processing. Recovering these discarded materials not only reduces waste but also provides a valuable source of bioactive substances that can add significant value to various industries. This study focuses on optimizing ultrasound-assisted aqueous extraction (UAE), a versatile and environmentally friendly technology, for recovering these pigments. UAE offers several advantages, including reduced solvent usage, operational simplicity, and the ability to preserve the biological activity of extracted compounds, making it suitable for industrial implementation. Our experimental approach utilized a full factorial design to evaluate the influence of key variables: solvent type (water, ethanol, and 50% ethanol-water) and extraction time (20, 30, and 40 minutes), while maintaining a constant temperature. Following extraction, a sequential process of filtration, hydrodistillation, and oven drying was performed to separate and purify the bioactive compounds. Results consistently showed extraction yields ranging between 9% and 12% across all samples. These findings underscore the potential of UAE as an efficient method for extracting valuable natural pigments from beetroot waste, contributing to a more sustainable agri-food chain and creating new avenues for high-value product development.

Modern diets are high in fructans, which may lead to abdominal discomfort, particularly in sensitive individuals. Microbial inulinase, an enzyme that hydrolyzes inulin into fructose and fructo-oligosaccharides (FOS), has significant prebiotic potential and may contribute to the prevention of metabolic disorders by enhancing fructan digestion.

This study investigates inulinase production by the Aspergillus niger ICCF 92 strain under various growth conditions. Three carbon sources (inulin, molasses, and carob pod decoction), the time required for biosynthesis processes, and stirring speed were evaluated for their influence on inulinase activity.

For inoculum development, the microorganism was grown in liquid malt extract medium for 5 days at 30 °C. Fermentations were conducted in 500 mL Erlenmeyer flasks with 100 mL of medium, under both static and stirring (220 rpm) conditions. Nitrogen sources included yeast extract, ammonium nitrate, and ammonium phosphate. Process monitoring included pH measurement, protein quantification via the Bradford assay, and inulinase activity assessment using the 3,5-dinitrosalicylic acid method.

The optimal inulinase production (38.29 U/mL) and protein concentration (0.7548 mg/mL) were achieved after 14 days of static fermentation with carob pod decoction as the carbon source.

These findings highlight the potential of A. niger ICCF 92 as a viable producer of inulinase and its possible application in mitigating metabolic and nutritional disorders through improved dietary fructan processing.

The Origanum vulgare L. ssp. glandulosum (Desf.), commonly known as glandular oregano, is a perennial herbaceous plant belonging to the Lamiaceae family. It is characterized by quadrangular, often branched stems, and opposite, oval to elliptical leaves rich in glandular structures. The flowers, ranging from pink to purple, are grouped in compact terminal inflorescences. This subspecies is endemic to Mediterranean regions, particularly Algeria and Tunisia, where it naturally grows in dry and sunny environments. It is valued for its strong aroma and medicinal properties, mainly attributed to the richness of its essential oil.

This study of plant aimed to evaluate the chemical composition and antibacterial and antioxidant activities of the essential oil extracted from O. vulgare ssp. glandulosum. Chemical analysis using gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS) identified 43 compounds representing 98.55% of the oil. The major constituents were para-cymene (25.615%), thymol (23.129%), and carvacrol (20.321%).

Antibacterial activity of essential oil of Origanum vulgare L.ssp. Glandulosum was assessed using the disk diffusion method by measuring inhibition zones and broth microdilution to determine minimum inhibitory concentrations (MIC). Results showed significant antimicrobial effects. Antioxidant activity was evaluated via the DPPH radical scavenging assay, demonstrating moderate antioxidant potential with an IC₅₀ value of 461.62 μg/ml.

Quorum sensing (QS) plays an essential role in biofilm formation, a critical, multi-step, and complex process in the development of dental plaque. QS regulates the expression of virulence factors, aggregation, and bacterial adhesion within the biofilm. Scientifically known as 4,1',6'-trichloro-4,1',6'-trideoxy-galacto-sucrose or 1,6-dichloro-1, 6-dideoxy-β-d-fructofuranosyl 4-chloro-4-deoxy-α-d-galacto-pyranoside, sucralose was synthesized by substituting three hydroxyl groups in sucrose at positions 4, 1', and 6' with chlorines. When compared to sucrose, sucralose is hundreds of times sweeter (approximately 600 times). Unlike sucrose, sucralose is a non-cariogenic artificial sweetener, commonly included in dental care products such as chewing gums, toothpastes, and mouthrinses to enhance palatability for consumers. While its non-cariogenic action is well established, there is limited evidence regarding the potential anti-cariogenic mechanisms of sucralose. This study investigated whether sucralose interferes with QS involved in oral bacterial biofilm formation. A representative LuxR-type quorum sensing regulator, LasR, was expressed in the presence of sucralose and/or its native ligand, N-acyl homoserine lactone (AHL). The expressed protein was purified using nickel-affinity chromatography and quantified by the Bradford assay. The findings reveal that sucralose significantly inhibits AHL-dependent signaling, presumably by disrupting receptor–ligand interactions. These results provide insights into a possible molecular mechanism underlying the anti-cariogenic action of sucralose, highlighting its potential as a functional additive in oral health formulations.

The global use of New Psychoactive Substances (NPS) has risen markedly in recent years. By the end of 2024, the European Union Drugs Agency (EUDA) had identified around 1000 NPS, including 47 newly detected compounds, 7 of which were synthetic cathinones. Representing the second-largest category of NPS, synthetic cathinones exhibit psychostimulant properties comparable to those of cocaine, amphetamines, and MDMA. The increasing misuse of these substances poses a significant public health risk due to their unclear pharmacology and well-established links to toxicity and fatalities, emphasizing the need for further biological investigation.

Given that synthetic cathinones are frequently consumed orally, this study investigates the impact on the protein profile of human intestinal Caco-2 epithelial cells following exposure to four synthetic cathinones: 3-CIC (3-chloro-N-isopropylcathinone), 4-CIC (4-chloro-N-isopropylcathinone), 3-Cl-TBC (3-chloro-terc-butylcathinone, commonly known as bupropion), and 4-Cl-TBC (4-chloro-terc-butylcathinone).

Preliminary protein analysis of Caco-2 cells exposed to synthetic cathinones revealed a general reduction in total protein content relatively to non-exposed controls, particularly with 3-CIC and 4-CIC. Among these, 3-CIC induced the most pronounced changes in protein expression, however showing an increased expression of proteins predominantly within the 40–50 kDa range.

These findings suggest an upregulation of several proteins, which was never reported. Given the increasing prevalence of synthetic cathinone abuse and the limited understanding of their toxicological profiles, these preliminary results highlight the need for further studies to identify the affected proteins and elucidate the cellular pathways affected by these substances of abuse.

In this study, we report an efficient and straightforward protocol for the synthesis of 1,2,3-trisubstituted triazoles catalyzed by an N-heterocyclic carbene (NHC)–Copper(I) complex. While numerous methods exist for constructing the triazole core, our approach uniquely combines operational simplicity with high regioselectivity and excellent catalytic efficiency. The desired triazole derivatives were obtained in consistently high yields ranging from 85% to 94%, demonstrating the robustness, reproducibility, and practical utility of the method.

NHCs have emerged as highly versatile ligands and organocatalysts, owing to their strong σ-donating ability, tunable steric profiles, and remarkable stability under a wide range of reaction conditions. In the context of copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions, NHC–Cu(I) complexes have shown superior catalytic performance by enhancing reaction rates, minimizing side reactions, and enabling mild, scalable reaction conditions. This catalytic system effectively facilitates the selective synthesis of 1,2,3-trisubstituted triazoles with a broad substrate scope and operational ease.

This work highlights the synthetic value of NHC–Cu(I) catalysis for the efficient construction of trisubstituted triazole frameworks, which serve as important scaffolds in medicinal chemistry, chemical biology, and materials science. The developed method provides a sustainable, user-friendly, and highly selective route for accessing these heterocycles, underscoring its potential for broad application in the synthesis of complex molecules and functional materials.

Heat transfer fluids (HTFs) play a crucial role across a broad range of industrial operations, absorbing and conveying thermal energy in applications such as process heating, metal fabrication, and machinery cooling—particularly within the aerospace, automotive, and marine sectors. HTFs serve as essential components in the generation of electricity through concentrating solar power systems. Here, they function as reservoirs of sensible heat, enabling thermal energy storage for use when direct solar radiation is unavailable, thereby ensuring continuous power conversion.

Previously, we have reported on the preparation of extended dibenzyl ethers as potential heat transfer fluids utilizing Williamson-type ether synthesis in combination with Suzuki reactions, often in one-pot reactions [1]. In the current contribution, we extend the scope of benzyl ethers that can be prepared under these conditions. Furthermore, we investigate the physical properties such as the heat capacity and the temperature-dependent density of selected dibenzyl ethers, and compare the values with computational data using incremental methods for the estimation of group contributions within the structures towards the macroscopic properties of the compounds. Finally, it was realized that while some of the dibenzyl ethers were stable even at 300 °C, studied benzyl ethers were found to degrade oxidatively in air at rt over longer time periods. Thus, after 365 days at rt dibenzyl ethers were found to have degraded to mixtures of benzaldehydes, benzoic acids and aryl benzoates. Possible mechanisms for these transformations are discussed.

[1] Thiemann et al., 3^rd World Sustainability Forum, Sciforum Electronic Conference Series, Vol. 3, 2013, d-002.