Correlation of Solubility Thermodynamics of Glibenclamide with Recrystallization and In Vitro Release Profile

The solubility of glibenclamide was evaluated in DMSO, NMP, 1,4-dioxane, PEG 400, Transcutol^® HP, water, and aqueous mixtures (T = 293.15~323.15 K). It was then recrystallized to solvate and compressed into tablets, of which 30-day stability and dissolution was studied. It had a higher solubility in 1,4-dioxane, DMSO, NMP (X_exp = 2.30 × 10³, 3.08 × 10⁴, 2.90 × 10⁴) at 323.15 K, its mixture (X_exp = 1.93 × 10³, 1.89 × 10⁴, 1.58 × 10⁴) at 298.15 K, and 1,4-dioxane (w) + water (1−w) mixture ratio of w = 0.8 (X_exp = 3.74 × 10³) at 323.15 K. Modified Apelblat (RMSD ≤ 0.519) and CNIBS/R-K model (RMSD ≤ 0.358) suggested good comparability with the experimental solubility. The minimum value of ΔG° vs ΔH° at 0.70 < x₂ < 0.80 suggested higher solubility at that molar concentration. Based on the solubility, it was recrystallized into the solvate, which was granulated and compressed into tablets. Among the studied solvates, the tablets of glibenclamide dioxane solvate had a higher initial (95.51%) and 30-day (93.74%) dissolution compared to glibenclamide reference (28.93%). There was no stability issue even after granulation, drying, or at pH 7.4. Thus, glibenclamide dioxane solvate could be an alternative form to improve the molecule’s properties.     

Absolute Antioxidant Activity of Five Phenol-Rich Essential Oils

Essential oils (EOs) have promising antioxidant activities which are gaining interest as natural alternatives to synthetic antioxidants in the food and cosmetic industries. However, quantitative data on chain-breaking activity and on the kinetics of peroxyl radical trapping are missing. Five phenol-rich EOs were analyzed by GC-MS and studied by oxygen-uptake kinetics in inhibited controlled autoxidations of reference substrates (cumene and squalene). Terpene-rich Thymus vulgaris (thymol 4%; carvacrol 33.9%), Origanum vulgare, (thymol 0.4%; carvacrol 66.2%) and Satureja hortensis, (thymol 1.7%; carvacrol 46.6%), had apparent k_inh (30 °C, PhCl) of (1.5 ± 0.3) × 10⁴, (1.3 ± 0.1) × 10⁴ and (1.1 ± 0.3) × 10⁴ M⁻¹s⁻¹, respectively, while phenylpropanoid-rich Eugenia caryophyllus (eugenol 80.8%) and Cinnamomum zeylanicum, (eugenol 81.4%) showed apparent k_inh (30 °C, PhCl) of (5.0 ± 0.1) × 10³ and (4.9 ± 0.3) × 10³ M⁻¹s⁻¹, respectively. All EOs already granted good antioxidant protection of cumene at a concentration of 1 ppm (1 mg/L), the duration being proportional to their phenolic content, which dictated their antioxidant behavior. They also afforded excellent protection of squalene after adjusting their concentration (100 mg/L) to account for the much higher oxidizability of this substrate. All investigated EOs had k_inh comparable to synthetic butylated hydroxytoluene (BHT) were are eligible to replace it in the protection of food or cosmetic products.     

Solubility and Thermodynamic Data of Febuxostat in Various Mono Solvents at Different Temperatures

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including “water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)” at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with “van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models”. The overall error values for van’t Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10⁻² in PEG-400 at 318.2 K, however the least one was 1.97 × 10⁻⁷ in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10⁻²) > THP (1.70 × 10⁻²) > 2-BuOH (1.38 × 10⁻²) > 1-BuOH (1.37 × 10⁻²) > IPA (1.10 × 10⁻²) > EtOH (8.37 × 10⁻³) > EA (8.31 × 10⁻³) > DMSO (7.35 × 10⁻³) > MeOH (3.26 × 10⁻³) > PG (1.88 × 10⁻³) > EG (1.31 × 10⁻³) > water (1.14 × 10⁻⁶) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was “endothermic and entropy-driven” in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility.     

Synthesis and Structure Elucidation of Novel Spirooxindole Linked to Ferrocene and Triazole Systems via [3 + 2] Cycloaddition Reaction

In the present work, a novel heterocyclic hybrid of a spirooxindole system was synthesized via the attachment of ferrocene and triazole motifs into an azomethine ylide by [3 + 2] cycloaddition reaction protocol. The X-ray structure of the heterocyclic hybrid (1″R,2″S,3R)-2″-(1-(3-chloro-4-fluorophenyl)-5-methyl-1H-1,2,3-triazole-4-carbonyl)-5-methyl-1″-(ferrocin-2-yl)-1″,2″,5″,6″,7″,7a″-hexahydrospiro[indoline-3,3″-pyrrolizin]-2-one revealed very well the expected structure, by using different analytical tools (FTIR and NMR spectroscopy). It crystallized in the triclinic-crystal system and the P-1-space group. The unit cell parameters are a = 9.1442(2) Å, b = 12.0872(3) Å, c = 14.1223(4) Å, α = 102.1700(10)°, β = 97.4190(10)°, γ = 99.1600(10)°, and V = 1484.81(7) ų. There are two molecules per unit cell and one formula unit per asymmetric unit. Hirshfeld analysis was used to study the molecular packing of the heterocyclic hybrid. H···H (50.8%), H···C (14.2%), Cl···H (8.9%), O···H (7.3%), and N···H (5.1%) are the most dominant intermolecular contacts in the crystal structure. O···H, N···H, H···C, F···H, F···C, and O···O are the only contacts that have the characteristic features of short and significant interactions. AIM study indicated predominant covalent characters for the Fe–C interactions. Also, the electron density (ρ(r)) at the bond critical point correlated inversely with the Fe–C distances.     

Pyrethroid and Etofenprox Resistance in Anopheles gambiae and Anopheles coluzzii from Vegetable Farms in Yaoundé, Cameroon: Dynamics,Intensity and Molecular Basis

Previous studies have indicated widespread insecticide resistance in malaria vector populations from Cameroon. However, the intensity of this resistance and underlying mechanisms are poorly known. Therefore, we conducted three cross-sectional resistance surveys between April 2018 and October 2019, using the revised World Health Organization protocol, which includes resistance incidences and intensity assessments. Field-collected Anopheles gambiae s.l. populations from Nkolondom, Nkolbisson and Ekié vegetable farms in the city of Yaoundé were tested with deltamethrin, permethrin, alpha-cypermethrin and etofenprox, using 1× insecticide diagnostic concentrations for resistance incidence, then 5× and 10× concentrations for resistance intensity. Subsamples were analyzed for species identification and the detection of resistance-associated molecular markers using TaqMan® qPCR assays. In Nkolbisson, both An. coluzzii (96%) and An. gambiae s.s. (4%) were found together, whereas only An. gambiae s.s. was present in Nkolondom, and only An. coluzzii was present in Ekié. All three populations were resistant to the four insecticides (<75% mortality rates―MR1×), with intensity generally fluctuating over the time between mod-erate (<98%―MR5×; ≥98%―MR10×) and high (76–97%―MR10×). The kdr L995F, L995S, and N1570Y, and the Ace-1 G280S-resistant alleles were found in An. gambiae from Nkolondom, at 73%, 1%, 16% and 13% frequencies, respectively, whereas only the kdr L995F was found in An. gambiae s.s. from Nkolbisson at a 50% frequency. In An. coluzzii from Nkolbisson and Ekié, we detected only the kdr L995F allele at 65% and 60% frequencies, respectively. Furthermore, expression levels of Cyp6m2, Cyp9k1, and Gste2 metabolic genes were highly upregulated (over fivefold) in Nkolondom and Nkolbisson. Pyrethroid and etofenprox-based vector control interventions may be jeopardized in the prospected areas, due to high resistance intensity, with multiple mechanisms in An. gambiae s.s. and An. coluzzii.     

Low Energy Electron Attachment by Some Chlorosilanes

In this paper, the rate coefficients (k) and activation energies (E_a) for SiCl₄, SiHCl₃, and Si(CH₃)₂(CH₂Cl)Cl molecules in the gas phase were measured using the pulsed Townsend technique. The experiment was performed in the temperature range of 298–378 K, and carbon dioxide was used as a buffer gas. The obtained k depended on temperature in accordance with the Arrhenius equation. From the fit to the experimental data points with function described by the Arrhenius equation, the activation energies (E_a) were determined. The obtained k values at 298 K are equal to (5.18 ± 0.22) × 10⁻¹⁰ cm³·s⁻¹, (3.98 ± 1.8) × 10⁻⁹ cm³·s⁻¹ and (8.46 ± 0.23) × 10⁻¹¹ cm³·s⁻¹ and E_a values were equal to 0.25 ± 0.01 eV, 0.20 ± 0.01 eV, and 0.27 ± 0.01 eV for SiHCl₃, SiCl₄, and Si(CH₃)₂(CH₂Cl)Cl, respectively. The linear relation between rate coefficients and activation energies for chlorosilanes was demonstrated. The DFT/B3LYP level coupled with the 6-31G(d) basis sets method was used for calculations of the geometry change associated with negative ion formation for simple chlorosilanes. The relationship between these changes and the polarizability of the attaching center (α_centre) was found. Additionally, the calculated adiabatic electron affinities (AEA) are related to the α_centre.     

Synthesis and Antibacterial Study of Novel Harmine Derivatives and Tetrahydro-β-Carboline Derivatives In Vitro

Dairy mastitis is a disease of dairy cattle caused by a variety of pathogenic microorganisms which has biought huge economic losses aused huge economic losses to the world. In this paper, Harmine derivatives and tetrahydro-β-carboline derivatives synthesized by the splice method are shown to have a good inhibitory effect on the pathogenic bacteria of dairy mastitis. The results of a bacteriostatic test on pathogenic bacteria of dairy cow mastitis (S. dysgalactiae, S. pyogenes, B. subtilis and P. vulgaris) showed that compound 7l had the best bacteriostatic effect on Streptococcus dysgalactiae, with a mic value of 43.7 μ g/mL. When the concentration of 7l was 1 × MIC and 2 × MIC, it had a significant inhibitory effect on Streptococcus dysgalactiae, and there was almost no growth of Streptococcus dysgalactiae at 4 × MIC. The binding properties of target compound 7l to amine oxidase [flavin-containing] A protein were simulated by the molecular docking technique. The ligand 7l achieved strong binding with the receptor through three hydrogen bonds. The hydrogen bonds were amino acid residues thr-52, arg-51 and ser-24, which are the main force for the compound to bind to active sites.     

A small-molecule organic ferroelectric with piezoelectric voltage coefficient larger than that of lead zirconate titanate and polyvinylidene difluoride

Piezoelectric materials that generate electricity when deforming are ideal for many implantable medical sensing devices. In modern piezoelectric materials, inorganic ceramics and polymers are two important branches, represented by lead zirconate titanate (PZT) and polyvinylidene difluoride (PVDF). However, PVDF is a nondegradable plastic with poor crystallinity and a large coercive field, and PZT suffers from high sintering temperature and toxic heavy element. Here, we successfully design a metal-free small-molecule ferroelectric, 3,3-difluorocyclobutanammonium hydrochloride ((3,3-DFCBA)Cl), which has high piezoelectric voltage coefficients g₃₃ (437.2 × 10⁻³ V m N⁻¹) and g₃₁ (586.2 × 10⁻³ V m N⁻¹), a large electrostriction coefficient Q₃₃ (about 4.29 m⁴ C⁻²) and low acoustic impedance z₀ (2.25 × 10⁶ kg s⁻¹ m⁻²), significantly outperforming PZT (g₃₃ = 34 × 10⁻³ V m N⁻¹ and z₀ = 2.54 × 10⁷ kg s⁻¹ m⁻²) and PVDF (g₃₃ = 286.7 × 10⁻³ V m N⁻¹, g₃₁ = 185.9 × 10⁻³ V m N⁻¹, Q₃₃ = 1.3 m⁴ C⁻², and z₀ = 3.69 × 10⁶ kg s⁻¹ m⁻²). Such a low acoustic impedance matches that of the body (1.38–1.99 × 10⁶ kg s⁻¹ m⁻²) reasonably well, making it attractive as next-generation biocompatible piezoelectric devices for health monitoring and “disposable” invasive medical ultrasound imaging.

A small-molecule organic ferroelectric (3,3-DFCBA)Cl has high piezoelectric voltage coefficients g₃₃ (437.2 × 10⁻³ V m N⁻¹), a large electrostriction coefficient Q₃₃, and low acoustic impedance z₀, far beyond that of PZT and PVDF.     

Layering Optimization of the SrFe0.9Ti0.1O3−δ–Ce0.8Sm0.2O1.9 Composite Cathode

Cathode thickness plays a major role in establishing an active area for an oxygen reduction reaction in energy converter devices, such as solid oxide fuel cells. In this work, we prepared SrFe_0.9Ti_0.1O_3−δ–Ce_0.8Sm_0.2O_1.9 composite cathodes with different layers (1×, 3×, 5×, 7×, and 9× layer). The microstructural and electrochemical performance of each cell was then explored through scanning electron microscopy and electrochemical impedance spectroscopy (EIS). EIS analysis showed that the area-specific resistance (ASR) decreased from 0.65 Ωcm² to 0.12 Ωcm² with the increase in the number of layers from a 1× to a 7×. However, the ASR started to slightly increase at the 9× layer to 2.95 Ωcm² due to a higher loss of electrode polarization resulting from insufficient gas diffusion and transport. Therefore, increasing the number of cathode layers could increase the performance of the cathode by enlarging the active area for the reaction up to the threshold point.     

The Effect of Growth Parameters on Electrophysical and Memristive Properties of Vanadium Oxide Thin Films

We have experimentally studied the influence of pulsed laser deposition parameters on the morphological and electrophysical parameters of vanadium oxide films. It is shown that an increase in the number of laser pulses from 10,000 to 60,000 and an oxygen pressure from 3 × 10⁻⁴ Torr to 3 × 10⁻² Torr makes it possible to form vanadium oxide films with a thickness from 22.3 ± 4.4 nm to 131.7 ± 14.4 nm, a surface roughness from 7.8 ± 1.1 nm to 37.1 ± 11.2 nm, electron concentration from (0.32 ± 0.07) × 10¹⁷ cm⁻³ to (42.64 ± 4.46) × 10¹⁷ cm⁻³, electron mobility from 0.25 ± 0.03 cm²/(V·s) to 7.12 ± 1.32 cm²/(V·s), and resistivity from 6.32 ± 2.21 Ω·cm to 723.74 ± 89.21 Ω·cm. The regimes at which vanadium oxide films with a thickness of 22.3 ± 4.4 nm, a roughness of 7.8 ± 1.1 nm, and a resistivity of 6.32 ± 2.21 Ω·cm are obtained for their potential use in the fabrication of ReRAM neuromorphic systems. It is shown that a 22.3 ± 4.4 nm thick vanadium oxide film has the bipolar effect of resistive switching. The resistance in the high state was (89.42 ± 32.37) × 10⁶ Ω, the resistance in the low state was equal to (6.34 ± 2.34) × 10³ Ω, and the ratio R_HRS/R_LRS was about 14,104. The results can be used in the manufacture of a new generation of micro- and nanoelectronics elements to create ReRAM of neuromorphic systems based on vanadium oxide thin films.     

Composition and Antimicrobial Activity of Ilex Leaves Water Extracts

Plants from the Ilex genus are known for properties such as antimicrobial and anti-inflammatory activity, can act as antiobesity agents and thus can be helpful in medicine. Some holly species, such as Ilex paraguariensis (widely known in the form of popular beverage: yerba mate), have been investigated, while others have been partially researched or remain unknown. Therefore, we performed qualitative and quantitative phytochemical analyses and screened antimicrobial properties of lesser-studied species (I. aquifolium L., I. aquifolium ‘Argentea Marginata’ and I. × meserveae ‘Blue Angel’). I. paraguariensis was used as a standard species for comparison purposes. Investigations were performed on water extracts due to their expected activity and composition. Antimicrobial research included evaluating minimal inhibitory, bactericidal (Staphylococcus aureus and Escherichia coli) and fungicidal concentration (Candida albicans, Alternaria alternata, Fusarium oxysporum, and Aspergillus niger) of extracts. The influence of the extracts on the production, eradication, and viability of bacterial biofilms was also analysed. It was established that Ilex paraguariensis possesses the richest profile of hydroxycinnamic acids derivatives in terms of component concentration and diversity. Ilex spp., especially I. × meserveae, contain a slightly higher amount of flavonoids and more different flavonoid derivatives than I. paraguariensis. However, the strongest antibacterial activity was shown by I. aquifolium L. and its cultivar ‘Argentea Marginata’ in terms of minimal inhibitory, bactericidal and fungicidal concentration, and biofilm assays. Extracts from both species significantly reduced the biofilm viability of S. aureus as well, which may be of use in the production of multicomponent lavaseptics, antiseptics, diuretics (supporting urinary tract infection therapy) and, due to their action on fungi, additives to growth media for specific fungi. The significant content of saponins enables Ilex extracts to be used as natural emulsifiers, for example, in cosmetics. Moreover, relatively high chlorogenic acid and rutin content may suggest use of Ilex spp. to treat obesity, digestive problems, in chemoprevention, and as preservatives in the food industry.     

Enzyme repurposing of a hydrolase as an emergent peroxidase upon metal binding

As an alternative to Darwinian evolution relying on catalytic promiscuity, a protein may acquire auxiliary function upon metal binding, thus providing it with a novel catalytic machinery. Here we show that addition of cupric ions to a 6-phosphogluconolactonase 6-PGLac bearing a putative metal binding site leads to the emergence of peroxidase activity (k_cat 7.8 × 10^–2 s^–1, K_M 1.1 × 10^–5 M). Both X-ray crystallographic and EPR data of the copper-loaded enzyme Cu·6-PGLac reveal a bis-histidine coordination site, located within a shallow binding pocket capable of accommodating the o-dianisidine substrate.     

Solubility Optimization of Loxoprofen as a Nonsteroidal Anti-Inflammatory Drug: Statistical Modeling and Optimization

Industrial-based application of supercritical CO₂ (SCCO₂) has emerged as a promising technology in numerous scientific fields due to offering brilliant advantages, such as simplicity of application, eco-friendliness, and high performance. Loxoprofen sodium (chemical formula C₁₅H₁₈O₃) is known as an efficient nonsteroidal anti-inflammatory drug (NSAID), which has been long propounded as an effective alleviator for various painful disorders like musculoskeletal conditions. Although experimental research plays an important role in obtaining drug solubility in SCCO₂, the emergence of operational disadvantages such as high cost and long-time process duration has motivated the researchers to develop mathematical models based on artificial intelligence (AI) to predict this important parameter. Three distinct models have been used on the data in this work, all of which were based on decision trees: K-nearest neighbors (KNN), NU support vector machine (NU-SVR), and Gaussian process regression (GPR). The data set has two input characteristics, P (pressure) and T (temperature), and a single output, Y = solubility. After implementing and fine-tuning to the hyperparameters of these ensemble models, their performance has been evaluated using a variety of measures. The R-squared scores of all three models are greater than 0.9, however, the RMSE error rates are 1.879 × 10⁻⁴, 7.814 × 10⁻⁵, and 1.664 × 10⁻⁴ for the KNN, NU-SVR, and GPR models, respectively. MAE metrics of 1.116 × 10⁻⁴, 6.197 × 10⁻⁵, and 8.777 × 10⁻⁵errors were also discovered for the KNN, NU-SVR, and GPR models, respectively. A study was also carried out to determine the best quantity of solubility, which can be referred to as the (x₁ = 40.0, x₂ = 338.0, Y = 1.27 × 10⁻³) vector.     

Study on the Joint Toxicity of BPZ,BPS, BPC and BPF to Zebrafish

Bisphenol Z (BPZ), bisphenol S (BPS), bisphenol C (BPC), and bisphenol F (BPF) had been widely used as alternatives to bisphenol A (BPA), but the toxicity data of these bisphenol analogues were very limited. In this study, the joint toxicity of BPZ, BPS, BPC, and BPF to zebrafish (Danio rerio) was investigated. The median half lethal concentrations (LC50) of BPZ, BPS, BPC, and BPF to zebrafish for 96 h were 6.9 × 10⁵ µM, 3.9 × 10⁷ µM, 7.1 × 10⁵ µM, and1.6 × 10⁶ µM, respectively. The joint toxicity effect of BPF–BPC (7.7 × 10⁵–3.4 × 10⁵µM) and BPZ–BPC (3.4 × 10⁵–3.5 × 10⁵µM) with the same toxic ratio showed a synergistic effect, which may be attributed to enzyme inhibition or induction theory. While the toxicity effect of the other two bisphenol analogue combined groups and multi-joint pairs showed an antagonistic effect due to the competition site, other causes need to be further explored. Meanwhile, the expression levels of the estrogen receptor genes (ERα, ERβ1) and antioxidant enzyme genes (SOD, CAT, GPX) were analyzed using a quantitative real-time polymerase chain reaction in zebrafish exposure to LC₅₀ of BPZ, BPS, BPC, and BPF collected at 24, 48, 72, and 96 h. Relative expression of CAT, GPX, and ERβ1 mRNA declined significantly compared to the blank control, which might be a major cause of oxidant injury of antioxidant systems and the disruption of the endocrine systems in zebrafish.     

Crystallography,Molecular Modeling,and COX-2 Inhibition Studies on Indolizine Derivatives

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC₅₀ of 5.84 µM, as compared to indomethacin (IC₅₀ = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 2₁/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)ų. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.     

Agaricus bisporus Crude Extract: Characterization and Analytical Application

In the present work crude Agaricus bisporus extract (ABE) has been prepared and characterized by its tyrosinase activity, protein composition and substrate specificity. The presence of mushroom tyrosinase (PPO3) in ABE has been confirmed using two-dimensional electrophoresis, followed by MALDI TOF/TOF MS-based analysis. GH27 alpha-glucosidases, GH47 alpha-mannosidases, GH20 hexosaminidases, and alkaline phosphatases have been also detected in ABE. ABE substrate specificity has been studied using 19 phenolic compounds: polyphenols (catechol, gallic, caffeic, chlorogenic, and ferulic acids, quercetin, rutin, dihydroquercetin, l-dihydroxyphenylalanine, resorcinol, propyl gallate) and monophenols (l-tyrosine, phenol, p-nitrophenol, o-nitrophenol, guaiacol, o-cresol, m-cresol, p-cresol). The comparison of ABE substrate specificity and affinity to the corresponding parameters of purified A. bisporus tyrosinase has revealed no major differences. The conditions for spectrophotometric determination have been chosen and the analytical procedures for determination of 1.4 × 10⁻⁴–1.0 × 10⁻³ M l-tyrosine, 3.1 × 10⁻⁶–1.0 × 10⁻⁴ M phenol, 5.4 × 10⁻⁵–1.0 × 10⁻³ M catechol, 8.5 × 10⁻⁵–1.0 × 10⁻³ M caffeic acid, 1.5 × 10⁻⁴–7.5 × 10⁻⁴ M chlorogenic acid, 6.8 × 10⁻⁵–1.0 × 10⁻³ M l-DOPA have been proposed. The procedures have been applied for the determination of l-tyrosine in food supplements, l-DOPA in synthetic serum, and phenol in waste water from the food manufacturing plant. Thus, we have demonstrated the possibility of using ABE as a substitute for tyrosinase in such analytical applications, as food supplements, medical and environmental analysis.     

Binding Interaction of Betulinic Acid to α-Glucosidase and Its Alleviation on Postprandial Hyperglycemia

Inhibiting the intestinal α-glucosidase can effectively control postprandial hyperglycemia for type 2 diabetes mellitus (T2DM) treatment. In the present study, we reported the binding interaction of betulinic acid (BA), a pentacyclic triterpene widely distributed in nature, on α-glucosidase and its alleviation on postprandial hyperglycemia. BA was verified to exhibit a strong inhibitory effect against α-glucosidase with an IC₅₀ value of 16.83 ± 1.16 μM. More importantly, it showed a synergistically inhibitory effect with acarbose. The underlying inhibitory mechanism was investigated by kinetics analysis, surface plasmon resonance (SPR) detection, molecular docking, molecular dynamics (MD) simulation and binding free energy calculation. BA showed a non-competitive inhibition on α-glucosidase. SPR revealed that it had a strong and fast affinity to α-glucosidase with an equilibrium dissociation constant (K_D) value of 5.529 × 10⁻⁵ M and a slow dissociation. Molecular docking and MD simulation revealed that BA bound to the active site of α-glucosidase mainly due to the van der Waals force and hydrogen bond, and then changed the micro-environment and secondary structure of α-glucosidase. Free energy decomposition indicated amino acid residues such as PHE155, PHE175, HIE277, PHE298, GLU302, TRY311 and ASP347 of α-glucosidase at the binding pocket had strong interactions with BA, while LYS153, ARG210, ARG310, ARG354 and ARG437 showed a negative contribution to binding affinity between BA and α-glucosidase. Significantly, oral administration of BA alleviated the postprandial blood glucose fluctuations in mice. This work may provide new insights into the utilization of BA as a functional food and natural medicine for the control of postprandial hyperglycemia.     

Comparative Analysis of Polycyclic Aromatic Hydrocarbons and Halogenated Polycyclic Aromatic Hydrocarbons in Different Parts of Perilla frutescens (L.) Britt.

Perilla frutescens (L.) Britt., a medicinal herb and edible plant, is very popular among East Asian countries. The perilla leaves, stems and seeds can be used as traditional medicines and foods. Polycyclic aromatic hydrocarbons (PAHs) and halogenated PAHs (HPAHs) are organic pollutants that are widely present in the environment, such as in water, air and soil, and are harmful to humans. In this study, the contents of 16 PAHs and 4 HPAHs in perilla leaves, stems and seeds were determined by gas chromatography tandem mass spectrometry (GC-MS). A total of 12 PAHs were detected in all samples, and no HPAHs were detected. The total contents of PAHs in perilla leaves, stems and seeds varied from 41.93 to 415.60 ng/g, 7.02 to 51.52 ng/g and 15.24 to 180.00 ng/g, respectively. The statistical analyses showed that there were significant differences in the distribution of PAHs in perilla leaves, stems and seeds. On the basis of the toxic equivalent quantity (TEQ) and incremental lifetime cancer risk (ILCR) model, the cancer risks of the intake of perilla leaves, stems and seeds were assessed to be from 3.30 × 10⁻⁸ to 2.11 × 10⁻⁵, 5.52 × 10⁻⁹ to 5.50 × 10⁻⁸ and 1.20 × 10⁻⁸ to 1.41 × 10⁻⁷, respectively. These were lower than 10⁻⁴ (the priority risk level of the EPA) and suggested that there may be almost no cancer risk from the intake of these traditional Chinese medicines (TCMs).     

Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains

The treatment of benzylidenemalononitriles with phenylhydrazines in refluxing ethanol did not provide pyrazole derivatives, but instead furnished hydrazones. The structure of hydrazones was secured by X-ray analysis. The chemical proof was also obtained by direct reaction of 3,4,5-trimethoxybenzaldehyde with 2,4-dichlorophenylhydrazine. Newly synthesized hydrazones were tested against eight Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC₉₉). Five compounds were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)), with MIC₉₉ values ranging from 16 to 32 µg/mL and selective antifungal activity over cytotoxicity.     

Spectrophotometric Study of Bridging N-Donor Ligand-Induced Supramolecular Assembly of Conjugated Zn-Trisporphyrin with a Triphenylamine Core

This article studies the supramolecular assembly behavior of a Zn-trisporphyrin conjugate containing a triphenylamine core (1) with bridging N-donor ligands using the UV-vis spectrophotometric titration method at micromolar concentrations. Our results show that pyridine, a non-bridging ligand, formed a 3:1 open complex with 1. The corresponding binding constant was estimated to be (2.7 ± 0.15) × 10¹⁴ M⁻³. In contrast, bridging ligands, 4,4-bipyridine (BIPY) and 1,3-di(4-pyridyl)propane (DPYP), formed stable 3:2 double-decker complexes with 1 in solution, which collapsed to yield a 3:1 open complex when excess BIPY or DPYP was added. The binding constants for forming BIPY and DPYP double-decker complexes were estimated to be (9.26 ± 0.07) × 10²⁷ M⁻⁴ and (3.62 ± 0.16) × 10²⁷ M⁻⁴, respectively. The UV-vis titration profiles supported the conclusion that the degradation of the 3:2 double-decker 1∙BIPY complex is less favorable compared to that of 1∙DPYP. Consequently, the formation of the 3:1 1∙DPYP open complex proceeded more readily than that of 1∙BIPY.