Molecules, Volume 28, Issue 20 (October-2 2023) – 234 articles

C. berlandieri ssp. berlandieri (C. berlandieri) is one of the most common members of the group of plants known as quelites, which are dark leafy greens widely consumed in Mexico. This study aimed to evaluate the impact of two drying procedures (oven drying and freeze-drying/lyophilization) on the polyphenolic composition, antioxidant capacity, and proximal chemical analysis of C. berlandieri leaves and inflorescences (raw or boiled). The results indicated that the raw freeze-dried samples had higher amounts (p < 0.05) of total phenolic compounds, total flavonoids, and antioxidant capacity, mainly in the inflorescence. The oven-dried samples showed an increased concentration of polyphenols after boiling, while the lyophilized samples showed a slightly decreased concentration. The drying process was observed to have little impact on the proximal chemical composition. Quantification by UPLC-DAD-ESI-QToF/MS identified up to 23 individual phenolic compounds, with freeze-dried samples showing higher amounts of individual compounds compared with oven-dried. Procyanidin B2 was found exclusively in the inflorescences. The inflorescences have a higher content of phenolic compounds and greater antioxidant capacity than the leaves. Regardless of the drying process, the leaves and inflorescences of C. berlandieri contain an interesting variety of phenolic compounds that may have beneficial effects on health. Full article

In this paper, the bio-based raw material erythritol was used to introduce an acetal structure into the benzoxazine resins. The benzoxazine-based resins containing an erythritol acetal structure could be degraded in an acidic solution and were environmentally friendly thermosetting resins. Compounds and resins were characterized by ¹H nuclear magnetic resonance (¹H NMR) and Fourier-transform infrared (FT-IR) analyses, and melting points were studied by a differential scanning calorimeter (DSC); the molecular weight was analyzed by gel permeation chromatography (GPC). The dynamic mechanical properties and thermal stability of polybenzoxazine resins were studied by dynamic mechanical thermal analysis (DMTA) and a thermogravimetric analyzer (TGA), respectively. The thermal aging, wet-heat resistance, and degradation properties of polybenzoxazine resins were tested. The results showed that the polybenzoxazine resins synthesized in this paper had good thermal-oxidative aging, and wet-heat resistance and could be completely degraded in an acidic solution (55 °C DMF: water: 1 mol/L hydrochloric acid solution = 5:2:4 (v/v/v)). Full article

Ergot alkaloids are secondary metabolites resulting from fungi of the genus Claviceps that have proven to be highly toxic. These mycotoxins commonly infect cereal crops such as wheat, rye, barley, and oats. Due to the increase worldwide consumption of cereal and cereal-based products, the presence of ergot alkaloids in food presents a concern for human safety. For this reason, it is essential to develop several analytical methods that allow the detection of these toxic compounds. This review compiles and discusses the most relevant studies and methods used in the detection and quantification of ergot alkaloids. Moreover, the decontamination techniques are also addressed, with special attention to sorting, cleaning, frying, baking, peeling, and ammonization methods, as they are the only ones already applied to ergot alkaloids. Full article

In this study, Cu-doped ZnO was prepared via the facile one-pot solvothermal approach. The structure and composition of the synthesized samples were characterized by XRD (X-ray diffraction), TEM (transmission electron microscopy), and XPS (X-ray photoelectron spectroscopy) analyses, revealing that the synthesized samples consisted of Cu-doped ZnO nanoparticles. Ultraviolet–visible (UV-vis) spectroscopy analysis showed that Cu-doping significantly improves the visible light absorption properties of ZnO. The photocatalytic capacity of the synthesized samples was tested via the disinfection of Escherichia coli, with the Cu-ZnO presenting enhanced disinfection compared to pure ZnO. Of the synthesized materials, 7% Cu-ZnO exhibited the best photocatalytic performance, for which the size was ~9 nm. The photocurrent density of the 7% Cu-ZnO samples was also significantly higher than that of pure ZnO. The antifungal activity for 7% Cu-ZnO was also tested on the pathogenic fungi of Fusarium graminearum. The macroconidia of F. graminearum was treated with 7% Cu-ZnO photocatalyst for 5 h, resulting in a three order of magnitude reduction at a concentration of 10⁵ CFU/mL. Fluorescence staining tests were used to verify the survival of macroconidia before and after photocatalytic treatment. ICP-MS was used to confirm that Cu-ZnO met national standards for cu ion precipitation, indicating that Cu-ZnO are environmentally friendly materials. Full article

Data on Henry’s law constants make it possible to systematize geochemical conditions affecting atmosphere status and consequently triggering climate changes. The constants of Henry’s law are desired for assessing the processes related to atmospheric contaminations caused by pollutants. The most important are those that are capable of long-term movements over long distances. This ability is closely related to the values of Henry’s law constants. Chemical changes in gaseous mixtures affect the fate of atmospheric pollutants and ecology, climate, and human health. Since the number of organic compounds present in the atmosphere is extremely large, it is desirable to develop models suitable for predictions for the large pool of organic molecules that may be present in the atmosphere. Here, we report the development of such a model for Henry’s law constants predictions of 29,439 compounds using the CORAL software (2023). The statistical quality of the model is characterized by the value of the coefficient of determination for the training and validation sets of about 0.81 (on average). Full article

Multicomponent reactions have emerged as an important approach for the synthesis of diverse and complicated chemical compounds. They have various advantages over two-component reactions, including the convenience of one-pot procedures and the ability to modify the structure of agents. Here, we employed in vitro and in silico studies to explore the anticancer potential of novel aminobenzylnaphthols derived from the Betti reaction (MMZ compounds). MTT assay was used to explore the cytotoxic activity of the compounds in pancreatic (BxPC-3 cells) and colorectal (HT-29) cancer cell lines or normal human lung fibroblasts (WI-38 cells). Proapoptotic properties of two derivatives MMZ-45AA and MMZ-140C were explored using AO/EB and annexin V-FITC/PI staining. In silico studies including ADMET profiling, molecular target prediction, docking, and dynamics were employed. The compounds exhibited cytotoxic properties and showed proapoptotic properties in respective IC₅₀ concentrations. As indicated by in silico investigations, anticancer activity of MMZs can be attributed to the inhibition of ADORA1, CDK2, and TRIM24. Furthermore, compounds exhibited favorable ADMET properties. MMZs constitute an interesting scaffold for the potential development of new anticancer agents. Full article

This research is based on the concept that mitochondria are a promising target for anticancer therapy, including thatassociated with the use of oxidative phosphorylation blockers (mitochondrial poisons). Liposomes based on L-α-phosphatidylcholine (PC) and cholesterol (Chol) modified with cationic surfactants with triphenylphosphonium (TPPB-n, where n = 10, 12, 14, and 16) and imidazolium (IA-n(OH), where n = 10, 12, 14, and 16) head groups were obtained. The physicochemical characteristics of liposomes at different surfactant/lipid molar ratios were determined by dynamic/electrophoretic light scattering, transmission electron microscopy, and spectrophotometry. The hydrodynamic diameter of all the systems was within 120 nm with a polydispersity index of no more than 0.24 even after 2 months of storage. It was shown that cationization of liposomes leads to an increase in the internalization of nanocontainers in pancreatic carcinoma (PANC-1) and duodenal adenocarcinoma (HuTu 80) cells compared with unmodified liposomes. Also, using confocal microscopy, it was shown that liposomes modified with TPPB-14 and IA-14(OH) statistically better colocalize with the mitochondria of tumor cells compared with unmodified ones. At the next stage, the mitochondrial poison rotenone (ROT) was loaded into cationic liposomes. It was shown that the optimal loading concentration of ROT is 0.1 mg/mL. The Korsmeyer–Peppas and Higuchi kinetic models were used to describe the release mechanism of ROT from liposomes in vitro. A significant reduction in the IC₅₀ value for the modified liposomes compared with free ROT was shown and, importantly, a higher degree of selectivity for the HuTu 80 cell line compared with the normal cells (SI value is 307 and 113 for PC/Chol/TPPB-14/ROT and PC/Chol/IA-14(OH)/ROT, respectively) occurred. It was shown that the treatment of HuTu 80 cells with ROT-loaded cationic liposomal formulations leads to a dose-dependent decrease in the mitochondrial membrane potential. Full article

The present work elucidates the fabrication of Barium Lanthanum Oxide nanosheets (BaLa₂O₄ NSs) via a simple one-pot precipitation method. The acquired results show an orthorhombic crystal system with an average crystallite size of 27 nm. The morphological studies revealed irregular-shaped sheets stacked together in a layered structure, with the confirmation of the precursor elements. The diffused reflectance studies revealed a strong absorption between 200 nm and 350 nm, from which the band-gap energy was evaluated to be 4.03 eV. Furthermore, the fluorescence spectrum was recorded for the prepared samples; the excitation spectrum shows a strong peak at 397 nm, attributed to the ⁴F_7/2→⁴G_11/2 transition, while the emission shows two prominent peaks at 420 nm (⁴G_7/2→⁴F_7/2) and 440 nm (⁴G_5/2→⁴F_7/2). The acquired emission results were utilized to confirm the color emission using a chromaticity plot, which found the coordinates to be at (0.1529 0.1040), and the calculated temperature was 3171 K. The as-prepared nanosheets were utilized in detecting latent fingerprints (LFPs) on various non-porous surfaces. The powder-dusting method was used to develop latent fingerprints on various non-porous surfaces, which resulted in detecting all the three ridge patterns. Furthermore, the as-synthesized nanosheets were used to degrade methyl red (MR) dye, the results of which show more than 60% degradation at the 70th minute. It was also found that there was no further degradation after 70 min. All the acquired results suggest the clear potential of the prepared BaLa₂O₄ NSs for use in advanced forensic and photocatalytic applications. Full article

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21β-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc–14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21β-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC₅₀) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 μg/mL, while compounds displayed IC₅₀ values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 μg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC₅₀ 2.50 ± 0.12 to 4.78 ± 0.36 μg/mL; compounds IC₅₀ 2.93 ± 0.02 to 50.97 ± 0.37 μg/mL) with selectivity indices greater than 10 (SI_Dd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21β-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21β-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa. Full article

Isoxaflutole and atrazine are representative pesticides for weed control in corn fields. Formulations containing these two pesticides have been registered in China, and their residues may threaten food safety and human health. In this study, a method for simultaneous determination of isoxaflutole, atrazine, and their metabolites in fresh corn, corn kernels, and corn straw was established based on modified QuEChERS pre-treatment and high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). The linearity of seven compounds was good (R² ≥ 0.9912), and the matrix effect was 48.5–77.1%. At four spiked levels of 0.01, 0.02, 0.05, and 0.5 mg kg⁻¹, all compounds’ average recovery was 76% to 116%, with relative standard deviation (RSD) less than 18.9%. Field experiments were conducted in Liaoning, Heilongjiang, Inner Mongolia, Shanxi, Beijing, and Yunnan provinces to study the terminal residues. The terminal residues of all compounds were below the LOQ (0.01 mg kg⁻¹) in fresh corn and corn kernels, and atrazine residues in corn straw ranged from <0.05 mg kg⁻¹ to 0.17 mg kg⁻¹. Finally, a dietary risk assessment was conducted based on residues from field trials, food consumption, and acceptable daily intake (ADI). For all populations, the chronic dietary risk probability (RQ_c) of atrazine was between 0.0185% and 0.0739%, while that of isoxaflutole was 0.0074–0.0296%, much lower than 100%. The results may provide scientific guidance for using isoxaflutole and atrazine in corn field ecosystems. Full article

Controlling flavor perception by analyzing volatile and taste compounds is a key challenge for food industries, as flavor is the result of a complex mix of components. Machine-learning methodologies are already used to predict odor perception, but they are used to a lesser extent to predict aroma perception. The objectives of this work were, for the processed cream cheese models studied, to (1) analyze the impact of the composition and process on the sensory perception and VOC release and (2) predict “fresh cream” aroma perception from the VOC characteristics. Sixteen processed cream cheese models were produced according to a three-factor experimental design: the texturing agent type (κ-carrageenan, agar-agar) and level and the heating time. A R-A-T-A test on 59 consumers was carried out to describe the sensory perception of the cheese models. VOC release from the cheese model boli during swallowing was investigated with an in vitro masticator (Oniris device patent), followed by HS-SPME-GC-(ToF)MS analysis. Regression trees and random forests were used to predict “fresh cream” aroma perception, i.e., one of the main drivers of liking of processed cheeses, from the VOC release during swallowing. Agar-agar cheese models were perceived as having a “milk” odor and favored the release of a greater number of VOCs; κ-carrageenan samples were perceived as having a “granular” and “brittle” texture and a “salty” and “sour” taste and displayed a VOC retention capacity. Heating induced firmer cheese models and promoted Maillard VOCs responsible for “cooked” and “chemical” aroma perceptions. Octa-3,5-dien-2-one and octane-2,3-dione were the two main VOCs that contributed positively to the “fresh cream” aroma perception. Thus, regression trees and random forests are powerful statistical tools to provide a first insight into predicting the aroma of cheese models based on VOC characteristics. Full article

As a new approach, pyrrolo[1,2-a]pyrazines were synthesized through the cyclization of 2-formylpyrrole-based enaminones in the presence of ammonium acetate. The enaminones were prepared with a straightforward method, reacting the corresponding alkyl 2-(2-formyl-1H-pyrrol-1-yl)acetates, 2-(2-formyl-1H-pyrrol-1-yl)acetonitrile, and 2-(2-formyl-1H-pyrrol-1-yl)acetophenones with DMFDMA. Analogous enaminones elaborated from alkyl (E)-3-(1H-pyrrol-2-yl)acrylates were treated with a Lewis acid to afford indolizines. The antifungal activity of the series of substituted pyrroles, pyrrole-based enaminones, pyrrolo[1,2-a]pyrazines, and indolizines was evaluated on six Candida spp., including two multidrug-resistant ones. Compared to the reference drugs, most test compounds produced a more robust antifungal effect. Docking analysis suggests that the inhibition of yeast growth was probably mediated by the interaction of the compounds with the catalytic site of HMGR of the Candida species. Full article

Branched-chain fatty acids (BCFAs) are natural components with a variety of biological activities. However, the regulation of lipid metabolism by BCFAs is unknown. It was dedicated to examining the impacts of BCFAs inferred from yak ghee on the expression of qualities related to lipid metabolism, natural pathways, and intestinal microbiota in mice. The treatment group (purified BCFAs from yak ghee) exhibited a decrease in cholesterol levels; a decrease in HMGCR levels; downregulation of FADS1, FADS2, ACC-α, FAS, GAPT4, GPAM, ACSL1, THRSP, A-FABP, and PPARα gene expression; and upregulation of SCD1, ACSS1, FABP1, CPT1, and DGAT-1 gene expression. Gut microbiota 16S rDNA sequencing analysis showed that the treatment group improved the gut microbiota by increasing the relative abundances and increasing the short-chain fatty acid levels produced by the genera Akkermansia, Clostridium, Lachnospiraceae, Lactobacillus, Anaerotaenia, and Prevotella. After adding BCFAs to cultured breast cancer cells, pathways that were downregulated were found to be related to fatty acid degradation and fatty acid metabolism, while 20 other pathways were upregulated. Our results suggest that BCFAs reduce body fat in mice by modulating intestinal flora and lipid metabolism and modulating fatty acid metabolism in breast cancer cells. Full article

Metalloenzymes make extensive use of manganese centers for oxidative catalysis, including water oxidation; the need to develop improved synthetic catalysts for these processes has long motivated the development of bioinspired manganese complexes. Herein, we report a series of bpy-(imidazole)_n (n = 1 or 2) (bpy = 2,2′-bipyridyl) ligands and their Mn²⁺ complexes. Four Mn²⁺ complexes are structurally characterized using single-crystal X-ray diffraction, revealing different tridentate and tetradentate ligand coordination modes. Cyclic voltammetry of the complexes is consistent with ligand-centered reductions and metal-centered oxidations, and UV-vis spectroscopy complemented by TD-DFT calculations shows primarily ligand-centered transitions with minor contributions from charge-transfer type transitions at higher energies. In solution, ESI-MS studies provide evidence for ligand reorganization, suggesting complex speciation behavior. The oxidation of the complexes in the presence of water is probed using cyclic voltammetry, but the low stability of the complexes in aqueous solution leads to decomposition and precludes their ultimate application as aqueous electrocatalysts. Possible reasons for the low stability and suggestions for improvement are discussed. Full article

Acalabrutinib, commercially known as Calquence^®, is a pharmacological molecule that has robust inhibitory activity against Bruton tyrosine kinase. The medicine in question was carefully developed by the esteemed pharmaceutical company AstraZeneca. The FDA granted authorization on 21 November 2019 for the utilization of acalabrutinib (ACB) in the treatment of small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL) in adult patients. The aim of this study was to develop a UPLC–MS/MS method that is effective, accurate, environmentally sustainable, and has a high degree of sensitivity. The methodology was specifically developed with the intention of quantifying ACB in human liver microsomes (HLMs). The methodology described above was subsequently utilized to assess the metabolic stability of ACB in HLMs in an in vitro environment. The validation procedures for the UPLC–MS/MS method in the HLMs were conducted in accordance with the bioanalytical method validation criteria established by the U.S.- DA. The utilization of the StarDrop software (version 6.6), which integrates the P450 metabolic module and DEREK software (KB 2018 1.1), was employed for the purpose of evaluating the metabolic stability and identifying potential hazardous alarms associated with the chemical structure of ACB. The calibration curve, as established by the ACB, demonstrated a linear correlation across the concentration range of 1 to 3000 ng/mL in the matrix of HLMs. The present study conducted an assessment of the accuracy and precision of the UPLC–MS/MS method in quantifying inter-day and intra-day fluctuations. The inter-day accuracy demonstrated a spectrum of values ranging from −1.00% to 8.36%, whilst the intra-day accuracy presented a range of values spanning from −2.87% to 4.11%. The t_1/2 and intrinsic clearance (Cl_int) of ACB were determined through in vitro testing to be 20.45 min and 39.65 mL/min/kg, respectively. The analysis concluded that the extraction ratio of ACB demonstrated a moderate level, thus supporting the recommended dosage of ACB (100 mg) to be administered twice daily for the therapeutic treatment of persons suffering from B-cell malignancies. Several computational tools have suggested that introducing minor structural alterations to the butynoyl group, particularly the alpha, beta-unsaturated amide moiety, or substituting this group during the drug design procedure, could potentially enhance the metabolic stability and safety properties of novel derivatives in comparison to ACB. Full article

Acne vulgaris stands out as the most prevalent skin disorder among teenagers and young adults, causing physical discomfort and considerable economic and psychological burdens on individuals and society. A wide range of topical and systemic therapies are available in acne treatment. Chemical peeling is a skin resurfacing technique designed to rebuild healthy skin using exfoliating substances, a simple and affordable process with various dermatological uses. Chemical peels, classified as superficial, medium, and deep, have been utilized for acne vulgaris and multiple other skin issues. In these chemical peels, a diverse range of chemical substances is employed, each with its unique mode of action. Among these, α-hydroxy and β-hydroxy acids have gathered attention for their efficacy in reducing acne lesions and enhancing overall skin appearance. Acids, such as salicylic acid, glycolic acid, or lactic acid, are commonly used in chemical peels due to their exfoliating and sebum-regulating properties. Despite the widespread use of these acids, there exists a lack of consensus regarding the most effective acid type and concentration for treating acne-prone skin. This review aims to bridge this knowledge gap by evaluating the effectiveness and safety of various organic acids used in chemical peels specifically for acne-prone skin. The findings of this comprehensive bibliographic review indicate that organic acid-based chemical peels represent effective and safe treatment options for individuals with acne-prone skin. Their adaptability sets these treatments apart; the choice of organic acid can be tailored to meet individual patient needs and tolerability levels. This personalized approach ensures that patients receive optimal care while minimizing the risks associated with the treatment. As research in this field progresses, it is anticipated that a more nuanced understanding of the ideal acid type and concentration will emerge, further enhancing the efficacy and safety of chemical peels for acne-prone skin. Full article

The progressive trend of utilizing bioactive materials constitutes diverse materials exhibiting biocompatibility. The innovative aspect of this research is the tuning of the thermo-mechanical behavior of polyurethane (PU) composites with improved biocompatibility for vibrant applications. Polycaprolactone (CAPA) Mn = 2000 g-mol⁻¹ was used as a macrodiol, along with toluene diisocyanate (TDI) and hexamethylene diisocyanate (HMDI), to develop prepolymer chains, which were terminated with 1,4 butane diol (BD). The matrix was reinforced with various concentrations of chitosan (1–5 wt %). Two series of PU composites (PUT/PUH) based on aromatic and aliphatic diisocyanate were prepared by varying the hard segment (HS) ratio from 5 to 30 (wt %). The Fourier-transformed infrared (FTIR) spectroscopy showed the absence of an NCO peak at 1730 cm⁻¹ in order to confirm polymer chain termination. Thermal gravimetric analysis (TGA) showed optimum weight loss up to 500 °C. Dynamic mechanical analysis (DMA) showed the complex modulus (E*) ≥ 200 MPa. The scanning electron microscope (SEM) proved the ordered structure and uniform distribution of chain extender in PU. The hemolytic activities were recorded up to 15.8 ± 1.5% for the PUH series. The optimum values for the inhibition of biofilm formation were recorded as 46.3 ± 1.8% against E. coli and S. aureus (%), which was supported by phase contrast microscopy. Full article

KP46 (tris(hydroxyquinolinato)gallium(III)) is an experimental, orally administered anticancer drug. Its absorption, delivery to tumours, and mode of action are poorly understood. We aimed to gain insight into these issues using gallium-67 and gallium-68 as radiotracers with SPECT and PET imaging in mice. [⁶⁷Ga]KP46 and [⁶⁸Ga]KP46, compared with [⁶⁸Ga]gallium acetate, were used for logP measurements, in vitro cell uptake studies in A375 melanoma cells, and in vivo imaging in mice bearing A375 tumour xenografts up to 48 h after intravenous (tracer level) and oral (tracer and bulk) administration. ⁶⁸Ga was more efficiently accumulated in A375 cells in vitro when presented as [⁶⁸Ga]KP46 than as [⁶⁸Ga]gallium acetate, but the reverse was observed when intravenously administered in vivo. After oral administration of [^68/67Ga]KP46, absorption of ⁶⁸Ga and ⁶⁷Ga from the GI tract and delivery to tumours were poor, with the majority excreted in faeces. By 48 h, low but measurable amounts were accumulated in tumours. The distribution in tissues of absorbed radiogallium and octanol extraction of tissues suggested trafficking as free gallium rather than as KP46. We conclude that KP46 likely acts as a slow releaser of gallium ions which are inefficiently absorbed from the GI tract and trafficked to tissues, including tumour and bone. Full article

Solubility is one of the most important physicochemical properties due to its involvement in physiological (bioavailability), industrial (design) and environmental (biotoxicity) processes, and in this regard, cosolvency is one of the best strategies to increase the solubility of poorly soluble drugs in aqueous systems. Thus, the aim of this research is to thermodynamically evaluate the dissolution process of triclocarban (TCC) in cosolvent mixtures of {N-methyl-2-pyrrolidone (NMP) + water (W)} at seven temperatures (288.15, 293.15, 298.15, 303.15, 308.15, 313.15 and 318.15 K). Solubility is determined by UV/vis spectrophotometry using the flask-shaking method. The dissolution process of the TCC is endothermic and strongly dependent on the cosolvent composition, achieving the minimum solubility in pure water and the maximum solubility in NMP. The activity coefficient decreases from pure water to NMP, reaching values less than one, demonstrating the excellent positive cosolvent effect of NMP, which is corroborated by the negative values of the Gibbs energy of transfer. In general terms, the dissolution process is endothermic, and the increase in TCC solubility may be due to the affinity of TCC with NMP, in addition to the water de-structuring capacity of NMP generating a higher number of free water molecules. Full article

This work aimed to study the influence of the polybutylene succinate (PBS) content on the physical, thermal, mechanical, and chemical properties of the obtained polylactic acid (PLA)/PBS composite fibers. PLA/PBS blend fibers were prepared by a simple melt-blown process capable of yielding nanofibers. Morphological analysis revealed that the fiber size was irregular and discontinuous in length. Including PBS affected the fiber size distribution, and the fibers had a smoother surface with increased amounts of added PBS. Differential scanning calorimetry analysis (DSC) revealed that the crystallization temperature of the PLA sheet (105.8 °C) was decreased with increasing PBS addition levels down to 91.7 °C at 10 wt.% PBS. This suggests that the addition of PBS may affect PLA crystallization, which is consistent with the X-ray diffraction analysis that revealed that the crystallinity of PLA (19.2%) was increased with increasing PBS addition up to 28.1% at 10 wt% PBS. Moreover, adding PBS increased the tensile properties while the % elongation at break was significantly decreased. Full article

The present study investigates four iron(II/III) porphyrazines with extending pyrrolyl peripheral substituents to understand the impact of introduced phenyl rings on the macrocycle’s electrochemical and spectroelectrochemical properties as well as their activity in oxidation reactions. The electrochemical studies showed six well-defined redox processes and quasi-reversible one-electron transfers—two originating from the iron cation and four related to the ring. Adding phenyl rings to the periphery increased the electrochemical gap by 0.1 V. The UV–Vis spectra changes were observed at the applied potential of −1.3 V with the presence of additional red-shifted bands. The oxidizing studies showed increased efficiency in the oxidation reaction of the reference substrate in the cases of Pz1 and Pz2 in both studied oxygen atom donors. The calculated reaction rates in t-BuOOH were 12.0 and 15.0 mmol/min, respectively, for Pz1 and Pz2, compared to 6.4 for Pz3 and 1.8 mmol/min for Pz4. The study identified potential applications for these porphyrazines in mimicking cytochrome P450 prosthetic groups for oxidation and hydroxylation reactions in the future. Full article

We have prepared and characterized two Ru(III) compounds based on the 2,2′-biimidazole (H₂biim) ligand, namely, a single complex of formula cis-[RuCl₂(H₂biim)₂]Cl·4H₂O (1) and a racemic mixture of formula {cis-[RuCl₂(H₂biim)₂]Cl}₂·4H₂O (2), which contains 50% of Ru(III) complex 1. Both compounds crystallize in the monoclinic system with space groups C2 and P2₁ for 1 and 2, respectively. These complexes exhibit the metal ion bonded to four nitrogen atoms from two H₂biim molecules and two chloride ions, which balance part of the positive charges in a distorted octahedral geometry. Significant differences are observed in their crystal packing, which leads to the observation of differences in their respective magnetic behaviors. Despite having imidazole rings in both compounds, π–π stacking interactions occur only in the crystal structure of 2, and the shortest intermolecular Ru···Ru separation in 2 is consequently shorter than that in 1. Variable-temperature dc magnetic susceptibility measurements performed on polycrystalline samples of 1 and 2 reveal different magnetic behaviors at low temperatures: while 1 behaves pretty much as a magnetically isolated mononuclear Ru(III) complex with S = 1/2, 2 exhibits the behavior of an antiferromagnetically coupled system with S = 0 and a maximum in the magnetic susceptibility curve at approximately 3.0 K. Full article

Wastewater contaminated with antibiotics is a major environmental challenge. The oxidation process is one of the most common and effective ways to remove these pollutants. The use of metal-free, green, and inexpensive catalysts can be a good alternative to metal-containing photocatalysts in environmental applications. We developed here the green synthesis of bio-graphenes by using natural precursors (Xanthan, Chitosan, Boswellia, Tragacanth). The use of these precursors can act as templates to create 3D doped graphene structures with special morphology. Also, this method is a simple method for in situ synthesis of doped graphenes. The elements present in the natural biopolymers (N) and other elements in the natural composition (P, S) are easily placed in the graphene structure and improve the catalytic activity due to the structural defects, surface charges, increased electron transfers, and high absorption. The results have shown that the hollow cubic Chitosan-derived graphene has shown the best performance due to the doping of N, S, and P. The Boswellia-derived graphene shows the highest surface area but a lower catalytic performance, which indicates the more effective role of doping in the catalytic activity. In this mechanism, O₂ dissolved in water absorbs onto the positively charged C adjacent to N dopants to create oxygenated radicals, which enables the degradation of antibiotic molecules. Light irradiation increases the amount of radicals and rate of antibiotic removal. Full article

This study was conducted to examine the chemical composition of the essential oils (EOs) from six Tunisian Eucalyptus species and to evaluate their anti-enzymatic and antibiofilm activities. The EOs were obtained through hydro-distillation of dried leaves and subsequently analyzed using GC/MS. The main class of compounds was constituted by oxygenated monoterpenes, particularly prominent in E. brevifolia (75.7%), E. lehmannii (72.8%), and E. woollsiana (67%). Anti-enzymatic activities against cholinesterases, α-amylase, and α-glucosidase were evaluated using spectrophotometric methods. Notably, the E. brevifolia, E. extensa, E. leptophylla, E. patellaris, and E. woollsiana EOs displayed potent acetylcholinesterase (AChE) inhibition (IC₅₀: 0.25–0.60 mg/mL), with E. lehmannii exhibiting lower activity (IC₅₀: 1.2 mg/mL). E. leptophylla and E. brevifolia showed remarkable α-amylase inhibition (IC₅₀: 0.88 mg/mL), while E. brevifolia and E. leptophylla significantly hindered α-glucosidase (IC₅₀ < 30 mg/mL), distinguishing them from other EOs with limited effects. Additionally, the EOs were assessed for their anti-biofilm properties of Gram-positive (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative (Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The E. extensa EO demonstrated the main antibiofilm effect against E. coli and L. monocytogenes with an inhibition > 80% at 10 mg/mL. These findings could represent a basis for possible further use of Eucalyptus EOs in the treatment of human microbial infections and/or as a coadjutant in preventing and treating Alzheimer’s disease and/or diabetes mellitus. Full article

Dextran, a variant of α-glucan with a significant proportion of α-(1,6) bonds, exhibits remarkable solubility in water. Nonetheless, the precipitation of dextran has been observed in injection vials during storage. The present study aimed to establish a technique for generating insoluble dextran and analyze its structural properties. Additionally, the potential for positively ionizing IS-dextran with polyethyleneimine was explored, with the ultimate objective of utilizing IS-dextran-PEI as a promising support for enzyme immobilization. As a result, IS-dextran was obtained by the process of slow evaporation with an average molecular weight of 6555 Da and a yield exceeding 60%. The calculated crystallinity of IS-dextran, which reaches 93.62%, is indicative of its irregular and dense structure, thereby accounting for its water insolubility. Furthermore, positive charge modification of IS-dextran, coupled with the incorporation of epichlorohydrin, resulted in all zeta potentials of IS-dextran-PEIs exceeding 30 mV, making it a promising supporting factor for enzyme immobilization. Full article

The clinical relationship between diabetes and inflammation is well established. Evidence clearly indicates that disrupting oxidant-antioxidant equilibrium and elevated lipid peroxidation could be a potential mechanism for chronic kidney disease associated with type 2 diabetes mellitus (T2DM). Under diabetic conditions, hyperglycemia, especially inflammation, and increased reactive oxygen species generation are bidirectionally associated. Inflammation, oxidative stress, and tissue damage are believed to play a role in the development of diabetes. Although the exact mechanism underlying oxidative stress and its impact on diabetes progression remains uncertain, the hyperglycemia-inflammation-oxidative stress interaction clearly plays a significant role in the onset and progression of vascular disease, kidney disease, hepatic injury, and pancreas damage and, therefore, holds promise as a therapeutic target. Evidence strongly indicates that the use of multiple antidiabetic medications fails to achieve the normal range for glycated hemoglobin targets, signifying treatment-resistant diabetes. Antioxidants with polyphenols are considered useful as adjuvant therapy for their potential anti-inflammatory effect and antioxidant activity. We aimed to analyze the current major points reported in preclinical, in vivo, and clinical studies of antioxidants in the prevention or treatment of inflammation in T2DM. Then, we will share our speculative vision for future diabetes clinical trials. Full article

A series of novel 2,6-diphenyl substituted imidazo[4,5-b]pyridines was designed and synthesized using optimized Suzuki cross coupling to evaluate their biological activity in vitro. The conditions of the Suzuki coupling were evaluated and optimized using a model reaction. To study the influence of the substituents on the biological activity, we prepared N-unsubstituted and N-methyl substituted imidazo[4,5-b]pyridines with different substituents at the para position on the phenyl ring placed at position 6 on the heterocyclic scaffold. Antiproliferative activity was determined on diverse human cancer cell lines, and the selectivity of compounds with promising antiproliferative activity was determined on normal peripheral blood mononuclear cells (PBMC). Pronounced antiproliferative activity was observed for p-hydroxy substituted derivatives 13 and 19, both displaying strong activity against most of the tested cell lines (IC₅₀ 1.45–4.25 μM). The unsubstituted N-methyl derivative 19 proved to be the most active derivative. There was a dose-dependent accumulation of G2/M arrested cells in several cancer cell lines after exposure to compound 19, implying a cell cycle-phase-specific mechanism of action. Additionally, the novel series of derivatives was evaluated for antiviral activity against a broad panel of viruses, yet the majority of tested compounds did not show antiviral activity. Full article

Sea fennel (Crithmum maritimum L.) is a strongly aromatic herb of the Apiaceae family, whose full exploitation by the modern food industry is of growing interest. This study aimed at investigating the microbiological quality, volatile profile, and sensory traits of sea fennel spices produced using room-temperature drying, oven drying, microwave drying, and freeze drying. All the assayed methods were able to remove moisture up until water activity values below 0.6 were reached; however, except for microwave drying, none of the assayed methods were effective in reducing the loads of contaminating microorganisms. The metataxonomic analysis highlighted the presence of phytopathogens and even human pathogens, including members of the genera Bacillus, Pseudomonas, Alternaria, and Cryptococcus. When compared to fresh leaves, dried leaves showed increased L* (lightness) and c* (chroma, saturation) values and reduced hue angle. Dried leaves were also characterized by decreased levels of terpene hydrocarbons and increased levels of aldehydes, alcohols, and esters. For the sensory test, the microwave-dried samples obtained the highest appreciation by the trained panel. Overall, the collected data indicated microwave drying as the best option for producing sea fennel spices with low microbial loads, brilliant green color, and high-quality sensory traits. Full article

The aim of this study was to develop and optimize a chiral HPLC-MS/MS method for quantitative analysis of (R)-/(S)-salbutamol and (R)-/(S)-salbutamol-4′-O-sulfate in human urine to allow for bioanalytical quantitation of the targeted analytes and investigations of stereoselectivity in the sulfonation pathway of human phase Ⅱ metabolism. For analytical method development, a systematic screening of columns and mobile phases to develop a separation via enantiomerically selective high performance liquid chromatography was performed. Electrospray ionization settings were optimized via multiple-step screening and a full factorial design-of-experiment. Both approaches were performed matrix-assisted and the predicted values were compared. The full factorial design was superior in terms of prediction power and knowledge generation. Performing a longitudinal excretion study in one healthy volunteer allowed for the calculation of excretion rates for all four targeted analytes. For this proof-of-concept, either racemic salbutamol or enantiopure levosalbutamol was administered perorally or via inhalation, respectively. A strong preference for sulfonation of (R)-salbutamol for inhalation and peroral application was found in in vivo experiments. In previous studies phenol sulfotransferase 1A3 was described to be mainly responsible for salbutamol sulfonation in humans. Thus, in vitro and in silico investigations of the stereoselectivity of sulfotransferase 1A3 complemented the study and confirmed these findings. Full article