Search Results (123)

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article

Background: Method quantification limits are typically determined by measuring variability at blank level only, without accounting for the uncertainties associated with the parameters of the calibration function applied. Methods: A method for the determination of artificial sweeteners and caffeine in soft drinks was validated. The effect of chosen regression function on quantification limits was assessed, considering both trueness and precision. Results: The validated method exhibited heteroscedasticity for all analytes, which is common in experimental methods. A linear response was observed within the working range for sweeteners, while a quadratic regression was required for caffeine. Due to the heteroscedasticity nature of the responses, weighted regressions were necessary to obtain the lowest method quantification limits, allowing for accurate (i.e., unbiased and precise) estimates at the lower end of the calibration range. Under weighted conditions, the regression equations obtained, with an upper range set at 600 mg·L⁻¹, were as follows: y = 3.9 + 58.9x for acesulfame K; y = 0.8 + 185.1x for saccharin; y = 3.5 + 43.3x for aspartame, and y = −7 + 159x − 0.242x² for caffeine. The method quantification limits determined using weighted regressions were 2 mg·L⁻¹ for each analyte, whereas these limits increased to 20 mg·L⁻¹ when non-weighted regressions were applied. Conclusions: The choice of regression function for transforming instrumental signals into analyte concentrations significantly affects the determination of quantification limits, owing to the inherent heteroscedasticity of analytical and bioanalytical calibrations. Weighted regressions are essential for producing accurate estimates at lower concentration levels. Applying weighted regression in the context of heteroscedastic calibrations can lead to quantification limits that are more than 10 times lower than unweighted approaches. Full article

In order to achieve differentiated utilization of red raspberry fruit pulp, a widely targeted metabolomics analysis of pulp from two regions was performed to explore the effect of plateau environment on the accumulation of secondary metabolites of red raspberry. Ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS/MS), combined with principal component analysis and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA), was used to process the data and correlate them with the results of four antioxidant assays. Fourteen metabolites were characterized in the fruit pulp of Qinghai raspberries, and 618 up-regulated differential metabolites were found, which was 4.35 times higher than that of Yunnan. Flavonoids and phenolic acids were more abundant, with kaempferol-3-O-sambubioside being endemic to Qinghai, and saccharin-7-O-glucoside and rhamnocereus citrinus being endemic to Yunnan. Metabolic pathway enrichment analysis showed that the fruit pulp from the two regions differed significantly (p < 0.01) in ATP-binding cassette transporter (ABC transporter), purine metabolism, and so on. Antioxidant analysis showed that the Yunnan raspberries (Y-RP) were significantly superior to Qinghai raspberries (Q-RP) in terms of DPPH radical scavenging ability (DPPH) and ferric ion reducing/antioxidant power (FRAP), while Q-RP was significantly superior to Y-RP in terms of oxygen radical absorbance capacity (ORAC) and ABTS radical scavenging capacity (ABTS). This study showed that the plateau environment significantly promotes the accumulation of functional secondary metabolites of red raspberry, which provides a theoretical basis for the development of the functional components of plateau raspberry. Full article

The rearrangement of a total of 56 members of 22 series of orthogonally protected N-alkyl arylsulphonamides of general structure 4-XC₆H₄SO₂NR¹CO₂R² [X = H, CH₃, F, Cl, Br, CH₃O, CN, CF₃ or C(CH₃)₃; R¹ = CH₃, CH₂CH₃, CH₂CH₂CH₃, CH(CH₃)₂ or CH₂CH(CH₃)₂; R² = CH₃, C₂H₅ or C(CH₃)₃] when treated with lithium di-isopropylamide in tetrahydrofuran at −78 °C has been studied. The competition between directed ortho metalated rearrangement, to form 4-X-2-(R²O₂C)C₆H₃SO₂NHR¹ and the production of a substituted saccharin, is strongly influenced by the size of R¹ and R², especially in the series with X = CH₃. When R¹ = CH₃ or to a lesser degree, C₂H₅, formation of the saccharin competes to a significant extent, especially when the migrating group is CO₂CH₃ or CO₂C₂H₅. In contrast, when R¹ is a larger alkyl group, particularly if it is branched at either the α- or β-carbon atom [CH(CH₃)₂ or CH₂CH(CH₃)₂], the increased steric hindrance essentially prevents cyclisation, thus facilitating rearrangement to 4-X-2-(R²O₂C)C₆H₃SO₂NHR¹ in high yield. The size of the migrating CO₂R² group also exerts an effect on the competition between the reactions: when R² = C(CH₃)₃, clean rearrangement is possible even when R¹ = CH₃ in each series of X. These results have implications for further elaboration and rearrangement of 4-X-2-(R²O₂C)C₆H₃SO₂NHR¹ in order to prepare substituted saccharins containing a 6-CO₂R³ group. Full article

Background/Objectives: Artificial sweeteners (ASs) are food additives used to impart sweetness to various food products. Common sweeteners used individually or in combination include acesulfame-K, aspartame, cyclamate, saccharin, sucralose, and neotame. While traditionally considered harmless, emerging research suggest potential health implications. This study aims to analyze commonly consumed food products in Croatia for ASs presence, quantify four ASs, and estimate daily intake of ASs. Additionally, product labeling was assessed for compliance with Regulation 1169/2011 on food information to consumers. Methods: This study assessed the presence of acesulfame-K, aspartame, cyclamate, and saccharin dihydrate in 121 frequently consumed food products from the Croatian market using a high-performance liquid chromatography method. Based on obtained concentrations, data from a parallel consumption study, and existing literature on acceptable daily intake (ADI), we assessed exposure to ASs. Results: ASs were found in a substantial proportion of analyzed products, with multiple sweeteners often present in a single product. Specifically, ASs were detected in 74% of carbonated drinks, 54% of fruit juices, 86% of energy drinks, 70% of high-protein milk products, and 66% of chewing gums. Hypothetical consumption scenarios demonstrated that children, due to their low body mass, are at the highest risk of exceeding ADI values. Conclusions: The widespread presence of ASs in food products raises concerns about excessive intake, particularly among children who frequently consume soft drinks, instant beverages, and protein drinks. These findings highlight the need for further research into cumulative ASs exposure and its potential health effects, as well as the importance of public health strategies to regulate ASs consumption. Full article

Low-calorie and zero-calorie sweeteners are increasingly consumed as sugar substitutes in low-calorie and low-glycemic diets. This study evaluated the thermal decomposition kinetics of commercial sweetener samples. The natural sweetener samples presented more straightforward thermal decomposition profiles in a heating process, according to the following stability order: xylitol > erythritol > C1 (saccharin-based) > A1 (aspartame-based). The kinetic parameters were calculated using the ASTM E-698 method, indicating that the xylitol sample required the lowest energy to initiate the decomposition process. In contrast, the saccharin-based sample presented the highest activation energy value among all those analyzed. Full article

Prenatal alcohol exposure (PAE) is associated with long-term neurodevelopmental deficits resulting in impaired executive functioning and motor control. Intriguingly, PAE has been linked with an increased risk of transient systemic hypoxia–ischemia (TSHI), which alone results in suboptimal fetal growth and neurodevelopmental consequences. Here, using two translationally relevant preclinical models, we investigated the short-term and lasting effects of PAE and TSHI on the morphology of the medial prefrontal cortex (mPFC), a region important in executive function, and tested whether PAE interacts with TSHI to produce a distinct pattern of injury relative to either condition alone. The four experimental groups included sham (saccharin water, no TSHI), PAE (5% alcohol, no TSHI), TSHI (saccharin water, TSHI), and PAE+TSHI (5% alcohol, TSHI). Brains were extracted for Golgi–Cox staining at Postnatal Day 35 (P35) or P100 and processed for 3D Sholl analysis. The analysis of the mPFC at P35 showed no significant differences in the number of branches or dendritic length overall, although the impact of TSHI compared to alcohol was significant for both. There were no significant differences in the number of Sholl intersections overall at P35, although a sex difference was noted in PAE offspring. At P100, analysis of filament dendritic length and branching number was also significantly impacted by TSHI compared to alcohol. Interestingly, sex was also a significant factor when assessing the impact of alcohol. PAE and TSHI both had an insignificantly increased number of Sholl intersections at P100 compared to the control. The observed changes to dendritic complexity at P100 demonstrate altered neuronal morphology in the mPFC that endure into adulthood. Given the importance of the mPFC in executive functioning, these pilot data provide insight into morphological changes that may contribute to the neurobehavioral deficits observed following exposure to PAE and TSHI and highlight the need for additional investigations into this area. Full article

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice. Full article

Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for public use, with acceptable daily intake information available: aspartame, acesulfame-K, saccharin, sucralose, neotame, and advantame. However, the impacts of NAS on the gut microbiome have raised potential concerns, since sporadic research revealed NAS-induced microbial changes in the gastrointestinal tracts and alterations in the microbiome–host interactive metabolism. Methods: Given the fact that the gut microbiome influences kaleidoscopic physiological functions in host health, this review aimed to decipher the impacts of NAS on the gut microbiome by implementing a comprehensive two-stage literature analysis based on each NAS. Results: This review documented disturbed microbiomes due to NAS exposure to a maximal resolution of species level using taxonomic clustering analysis, and recorded metabolism alterations involved in gut microbiome–host interactions. Conclusions: The results elucidated that specific NAS exhibited discrepant impacts on the gut microbiome, even though overlapping on the genera and species were identified. Some NAS caused glucose tolerance impairment in the host, but the key metabolites and their underlying mechanisms were different. Furthermore, this review embodied the challenges and future directions of current NAS–gut microbiome research to inspire advanced examination of the NAS exposure–gut microbiome–host metabolism axis. Full article

A metal-free and Selectfluor-mediated selective oxidation reaction of benzo[d]isothiazol-3(2H)-ones in aqueous media is presented. This novel strategy provides a facile, green, and efficient approach to access important benzo[d]isothiazol-3(2H)-one-1-oxides with excellent yields and high tolerance to various functional groups. Furthermore, the purification of benzoisothiazol-3-one-1-oxides does not rely on column chromatography. Moreover, the preparation of saccharine derivatives has been achieved through sequential, double oxidation reactions in a one-pot aqueous media. Full article

A novel magnetic nanomaterial with Fe₃O₄ as the core, PS-DVB as the shell layer, and the surface modified with C18 (C18−PS−DVB−Fe₃O₄) had been synthesized by seeded emulsion polymerization. C18−PS−DVB−Fe₃O₄ retains the advantages of the chemical stability, large porosity, and uniform morphology of organic polymers and has the magnetic properties of Fe₃O₄. A simple, flexible, and efficient magnetic dispersive solid phase extraction (Mag-dSPE) method for the extraction of preservatives, sweeteners, and colorants in river water was established. C18−PS−DVB−Fe₃O₄ was used as an adsorbent for Mag-dSPE and was coupled with high-performance liquid chromatography (HPLC) to detect 11 food additives: acesulfame, amaranth, benzoic acid, tartrazine, saccharin sodium, sorbic acid, dehydroacetic acid, sunset yellow, allura red, brilliant blue, and erythrosine. Under the optimum extraction conditions, combined with ChromCoreTMAQC18 (5 μm, 4.6 × 250 mm), 20 mmol/L ammonium acetate aqueous solution and methanol were used as mobile phases, and the detection wavelengths were 240 nm and 410 nm. The limits of detection (LODs) of 11 food additives were 0.6–3.1 μg/L with satisfactory recoveries ranging from 86.53% to 106.32%. And the material could be reused for five cycles without much sacrifice of extraction efficiency. The proposed method has been used to determine food additives in river water samples, and results demonstrate the applicability of the proposed C18−PS−DVB−Fe₃O₄ Mag-dSPE coupled with the HPLC method to environment monitoring analysis. Full article

Background: The aqueous solubility of indomethacin, a poorly water-soluble anti-inflammatory drug, was enhanced by co-crystallization with co-formers. The co-crystals were characterized and compared by an X-ray diffraction (XRD) analysis, terahertz (THz) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. Methods: Indomethacin co-crystals with either amides (saccharin, nicotine amide, and urea) or amino acids (lysine and histidine) as co-formers were prepared through the solvent evaporation method. The co-crystals were characterized by XRD, THz, and FT-IR analyses, followed by solubility tests to examine the solubility enhancement. Results: Both the XRD and THz analyses were capable of distinguishing co-crystals from physical mixtures; however, the THz spectra were relatively simpler and clearer than the XRD analysis. Furthermore, the solubility of indomethacin was successfully increased by two to three times that of pure indomethacin after co-crystallization with the above five co-formers. Conclusion: Five kinds of indomethacin co-crystals (with enhanced solubility) were successfully prepared and confirmed by the three spectroscopy techniques, XRD, THz, and FT-IR. The identification of co-crystals was achieved by a THz analysis, giving relatively simpler and clearer spectra with less noise. Hence, in addition to an XRD analysis, a THz analysis (a non-destructive, non-ionizing radiative, and relatively rapid measurement technique which is convenient and safe to use) is a good alternative method to characterize co-crystals. Full article

Rats can condition cephalic-phase insulin responses (CPIRs) to specific sounds or times of the day that predict food availability. The present study asked whether mice can condition a CPIR to the flavor of sapid solutions that produce postoral glucose stimulation. To this end, we subjected C57BL/6 mice to one of six experimental protocols. We varied both the duration of the five training sessions (i.e., 23 h or 1 h) and the nature of the training solution. In Experiment 1, consumption of a 0.61% saccharin solution was paired with IG co-infusion of a 16% glucose solution. In Experiments 2–6, the mice consumed a training solution containing a mixture of 0.61% saccharin + 16% glucose, 32% sucrose, 32% maltodextrin, flavored 32% maltodextrin, or 16% maltodextrin. We subsequently asked whether consumption of any of these fluids conditioned a CPIR to a test solution that produced a similar flavor, but which did not elicit a CPIR in naïve mice. The mice did condition a CPIR, but only to the solutions containing 32% maltodextrin. We attribute this conditioning to postoral actions of the concentrated maltodextrin solutions. Full article

Sugar beet is an important sugar crop, and its roots are mainly used for processing raw materials to produce products such as sugar, molasses, and saccharin, as well as being used as fodder for livestock. BvCPD, a key enzyme gene for brassinosteroid (BR) synthesis, regulates the development of parenchyma cells and vascular bundles by promoting BR synthesis, which promotes the expansion of the sugar beet taproot and influences the growth, development, and yield of sugar beets. This study investigated the impact of BvCPD on the physiological metabolism of sugar beet utilizing BvCPD overexpression, silent, and wild-type (WT) lines. BvCPD increased the chlorophyll content and maximum photochemical efficiency and improved the photosynthetic characteristics of sugar beet leaves. Simultaneously, BvCPD increased the rate of sugar beet taproot respiration and ATP content by enhancing the activities of phosphoglycerate kinase, alcohol dehydrogenase, sucrose synthase, and sucrose synthase catabolism. Moreover, BvCPD induced changes in the sugar fraction content, which increased the sugar yield of a single plant. In addition, BvCPD promoted water absorption, nitrogen accumulation, and lignin/cellulose synthesis activities, facilitated by increased activities of phenylalanine ammonia-lyase, cinnamyl alcohol dehydrogenase, cellulose synthase, and protein serine/threonine phosphatases, providing the requisite energy and materials for sugar beet growth. These findings not only provide a new perspective for understanding the physiological mechanisms regulating the growth of sugar beets but also provide a theoretical basis for the future improvement of sugar beet varieties through molecular breeding techniques. Full article

Background: Insulin exerts a crucial impact on glucose control, cellular growing, function, and metabolism. It is partially modulated by nutrients, especially as a response to the intake of foods, including carbohydrates. Moreover, insulin can exert an anorexigenic effect when inserted into the hypothalamus of the brain, in which a complex network of an appetite/hunger control system occurs. The current literature review aims at thoroughly summarizing and scrutinizing whether insulin release in response to glucose exposure may be a better choice to control body weight gain and related diseases compared to the use of sucrose substitutes (SSs) in combination with a long-term, well-balanced diet. Methods: This is a comprehensive literature review, which was performed through searching in-depth for the most accurate scientific databases and applying effective and relevant keywords. Results: The insulin action can be inserted into the hypothalamic orexigenic/anorexigenic complex system, activating several anorexigenic peptides, increasing the hedonic aspect of food intake, and effectively controlling the human body weight. In contrast, SSs appear not to affect the orexigenic/anorexigenic complex system, resulting in more cases of uncontrolled body weight maintenance while also increasing the risk of developing related diseases. Conclusions: Most evidence, mainly derived from in vitro and in vivo animal studies, has reinforced the insulin anorexigenic action in the hypothalamus of the brain. Simultaneously, most available clinical studies showed that SSs during a well-balanced diet either maintain or even increase body weight, which may indirectly be ascribed to the fact that they cannot cover the hedonic aspect of food intake. However, there is a strong demand for long-term longitudinal surveys to effectively specify the impact of SSs on human metabolic health. Full article