Increased Water Solubility Research Articles

Viscosity, Degree of Polymerization, Water Uptake, and Water Solubility Studies on Experimental Dichloro-BisGMA-Based Dental Composites

The objective of this work was to investigate the advantages of using dichloro bisphenol A-glycidyl methacrylate (dCl-BisGMA) as a potential matrix for dental resin composites. A series of model composites containing 65 wt% resin (urethane dimethacrylate/triethylene glycol dimethacrylate/BisGMA as 1:3:1) and 35 wt% silanated silica were prepared. Thus, BisGMA was replaced by dCl-BisGMA as 0, 25, 50, and 100 wt% to obtain UTBC0, UTBC25, UTBC50, and UTBC100, respectively. The composites’ rheological properties, degree of double-bond conversion (DC), water sorption (WSP), and water solubility (WSL) were examined. The data revealed a statistically significant reduction in the complex viscosity of composites containing dCl-BisGMA, compared with UTBC0. No significant differences between DCs were detected (p < 0.05). A significant enhancement in the reduction of the dCl-BisGMA composite WSP was also detected, and conversely, WSL was increased. Although the viscosity, DC, and WSP characters were enhanced, a WSL increase is an undesirable development. However, WSL is supposedly caused by cyclization of small flexible chains, which is more likely to occur in the presence of hydrophobic monomers such as dCl-BisGMA and more prone to leaching than are crosslinked networks. We concluded that dCl-BisGMA is a monomer that could potentially be used as an alternative or in combination with traditional monomers, including BisGMA, in resin-based dental composites, and it deserves further investigation.

Can reaction with amino acid turn Dimefox or Fluoroacetamide to nontoxic derivative: in Silico Study

To answer the title question, two ways can be applied. The first way is the experimental methods through using multistep, various techniques, different chemicals, characterization instruments, time, cost, and environmental considerations, and in vitro–in vivo testing. The second way is in Silico calculation. In this path of working, all steps, instruments, testing, chemicals …etc. will be canceled and only evaluate the numerical results to qualify any chemical to be a drug. The above points encourage me to take a hypothetical reaction between two insecticides (Dimefox (D) and Fluoroacetamide (F)) and several amino acids (aspartic acid, glutamic acid, glycine, alanine, phenylalanine, valine, isoleucine, proline, and methionine). The resulted P-N or C-N derivatives were subjected to ADMET and Druglikeness predications. They showed various important notes like increasing water solubility, mutagen character of Ames test to all 20 compounds, non–inhibition predication to P-glycoprotein, non–inhibition character of CYP-2C19 and CYP-2C9 except F. Many of 20 compounds showed negative response to Mouse or Rat Carcinogenic test, TA100-10RLI, TA100-NA, TA1535-10RLI, and TA1535-NA beside low risk to hREG inhibition. The other calculated characters were varied with influence of polarity, surface area, hydrogen bonding, and molecular structure. So, if these 18 compounds, if they formed in any biological system or in lab, have a toxic character.

Expanding the Repertoire for "Large Small Molecules": Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers.

Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (3, ABBV-167) that confers significantly increased water solubility to venetoclax and, upon oral administration to healthy volunteers either as a solution or high drug-load immediate release tablet, extensively converts to the parent drug. Additionally, ABBV-167 demonstrated a lower food effect with respect to venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing.

Production and Characterization of Nontoxic and Biodegradable Chitosan–Ectomycorrhizal Fungi Spores Blend Films

The use of synthetic-based packaging materials can causes health and environmental problems. To overcome these problems, researchers have focused on natural polymers such as cellulose and chitosan, which are easily degradable in nature. Herein, biodegradable composite films were prepared for the first time by including Pisolithus arhizus spores (PS) known as earth-ball like fungus into the chitosan matrix. The obtained films were characterized by FTIR, TGA, XRD and SEM. Additionally, thickness, soil degradation, water solubility and antioxidant activity tests were done to learn more about the films. Also, the cytotoxicity effect of obtained films against L929 fibroblast cells was studied. A gradual increase was recorded in the thermal stability and antioxidant activity of chitosan/PS composite films. It was observed that the addition of PS significantly increased water solubility compared to the control film (90%). In addition, the reduction of the biodegradation time of the composite films obtained has been confirmed to depend on the PS content. All films had no cytotoxic effects on L929 cells at 24 h and 72 h (all values > 70%). Considering the successful results in the production of chitosan–PS composite films, it is predicted that such production may be a biological alternative that can replace petroleum-based synthetic polymers.

Experimental and computational insight of the supramolecular complexes of Irbesartan with β-cyclodextrin based nanosponges

Irbesartan (IRB), one of the extensively prescribed drugs, for treatment of hypertension has limited therapeutic potential attributed to its poor water solubility, slow dissolution rate and poor bioavailability. Cyclodextrin-based nanosponges (NSs) are novel nanosized delivery systems comprised of hyper-crosslinked solid nanoparticles with nanosized cavities. Nanosponges are widely explored to increase water solubility of active drug moieties, to protect labile actives, to achieve prolonged or sustained release and site-specific targeting. The aim of the study was to investigate enhancement of solubility of Irbesartan by its complexation with β-cyclodextrin (β–CD) based nanosponges (NS). Blank NSs were fabricated by reacting β–CD, with pyromellitic dianhydride (PMDA) and diphenyl carbonate (DPC) as cross linkers, in various molar ratios of 1:2, 1:4, 1:6 and 1:8. Solubility studies were performed to select drug nanosponge stoichiometric complex with highest degree of saturation solubilization. Irbesartan loaded nanosponges namely PMDA-CDNS and DPC–CDNS were prepared and characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, powdered X-ray diffraction, scanning electron microscopy and nuclear magnetic resonance studies, to confirm the complexation of Irbesartan with nanosponges. PXRD studies revealed the shift from crystalline nature of Irbesartan to amorphous form in nanoponges. The average particle sizes of IRB–PMDA-CDNS and IRB-DPC-CDNS were 471.5 nm and 382.7 nm respectively. Zeta Potential values were 34.9 mV and −29mV for IRB–PMDA-CDNS and IRB- DPC-CDNS respectively. Entrapment efficiency varied from 9 to 38% w/w and 17 to 33%w/w for IRB–PMDA-CDNS and IRB-DPC-CDNS respectively. Complexation of IRB with β-cyclodextrin based nanosponges, as IRB-PMDA-CDNS and IRB-DPC-CDNS, resulted in significant enhancement of 81.86 and 23.35 folds, in its water solubility and 1.91- and 1.96-folds enhancement in its percent dissolution efficiency (% D.E.) respectively. Molecular docking calculations of IRB with DPC-CDNS and PMDA-CDNS have exhibited binding affinities of −8.97 and −9.51 kcal/mol respectively. Molecular dynamics simulations have revealed that IRB with PMDA-CDNS is more stable and efficient nanocarrier.

Pillararene-based supramolecular systems for theranostics and bioapplications

As an emerging type of important macrocycles for supramolecular chemistry, pillararenes and their derivatives have been widely studied and applied in numerous fields, which intensively promotes the development of chemistry, materials science and biology. Pillararene-based theranostic systems are of special interest in the biological and medical areas as they have shown very promising results. Owing to easy preparation, reliable guest affinity, good biocompatibility and stability, pillararenes are frequently used to construct functional biomaterials. On one hand, pillararenes can either be used individually or form diversiform self-assemblies such as micelles, nanoparticles and vesicles to increase water solubility and biocompatibility of drugs. On the other hand, it is promising to modify solid materials like framework materials, silica nanoparticles and graphene oxides with pillararene derivatives to enhance their functions and controllability. In this review, we summarize recent endeavors of pillararene-based supramolecular systems with theranostics and other biological applications comprising drug delivery/chemotherapy, photodynamic/photothermal therapy, antimicrobials, bioimaging, etc. By introducing several typical examples, the design principles, preparation strategies, identifications and bio-applications of these pillararene-based supramolecular systems are described. Future challenges and directions of this field are also outlined.

COMPLEX COMPOUNDS BASED ON PINOSTROBIN OXIME

The article studied the structural features of solid dispersions of pinostrobin oxime with arabinogalactan, disodium salt of glycyrrhizic acid, polyvinylpyrrolidone and basic magnesium carbonate obtained by mechanochemical treatment. The obtained complexes of pinostrobin oxime with arabinogalactan, disodium salt of glycyrrhizic acid, polyvinylpyrrolidone, and basic magnesium carbonate have increased water solubility in comparison with the initial pinostrobin oxime. The thermal effects of pinostrobin oxime and its complex compounds have been studied by differential scanning calorimetry. At the same time, on the DSC-curve, the melting peak of solid dispersions of pinostrobin oxime with disodium salt of glycyrrhizated acid and pinostrobin oxime with arabinogalactan is not displayed, which is associated with the intermolecular interaction of the components of the complex, where the molecule of pinostrobin oxime forms a bond with a complexformation agent during mechanochemical treatment. The complex of pinostrobin oxime with magnesium carbonate is not formed, as evidenced by the thermal curve, where the melting of the sample begins at 182 °C, and complete destruction occurs at a temperature of 782 °C, which is similar to the melting peak of the initial pinostrobin oxime. The results of studying intermolecular bonds in complexes of pinostrobin oxime by the method of NMR-relaxation indicate that the times of spin-lattice and spin-spin relaxation are very sensitive to intermolecular interaction and to the diffusion mobility of molecules.

IMPROVING SOLUBILITY AND DISSOLUTION OF A NATURAL PRODUCT APIGENIN VIA PREPARATION OF SOLID DISPERSION BY HOT MELT EXTRUSION

Objective: Hot Melt Extrusion (HME) is one of the techniques for preparing a solid dispersion hydrophilic excipient known as a no solvents practical method to increase the solubility of drugs. Apigenin (APG) has properties that thermal stable with melting point 345-350 °C but very low solubility in the water around 1,35 µg/ml. The polymer is stable in the HME method are Soluplus and Kollidon VA 64. The study aims to optimize the kind of polymer in HME formulae to improve the solubility and dissolution rate of apigenin by solid dispersion using hot-melt extrusion.
 Methods: Apigenin 10–50% w/w and Kollidon®VA 64 or Soluplus® and combination of Kollidon®VA 64 and Soluplus® were mixed, and the resulting blends extruded using a twin-screw extruder (Teach-Line ZK25T). Characterization of apigenin extrudates conducted using scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry, and dissolution.
 Results: Solubility studies presented enhancement in apigenin of 10%/Soluplus®90%; 10% w/w apigenin/Kollidon®VA 64 (90%); and 33,3% w/w apigenin/Kollidon®VA 64 33,3% mix Soluplus® 33,3% increased more than 18,25; 16,18-and 8,52-fold in water, respectively. Furthermore dissolution studies showed enhancement in apigenin percent release of 10%/Soluplus®90%; 10% w/w apigenin/Kollidon®VA 64 90%; and 33,3% w/w apigenin/Kollidon®VA 64 33,3% mix Soluplus® 33,3% tablet apigenin HME up to 34,29%; 69,75% and 30,69%, respectively.
 Conclusion: The formulation of 10% w/w Apigenin and 90% Soluplus® using hot-melt extrusion able to increase water solubility approximately 18,25-fold than raw material apigenin.

Salinity‐ and Heat‐Tolerant VES (Viscoelastic Surfactant) Clean Fracturing Fluids Strengthened by a Hydrophobic Copolymer with Extremely Low Damage

AbstractAs good thickeners for clean fracturing fluids, high salt‐tolerant surfactants have received increasing attention. Based on previous studies, we have further studied the performances of four surfactants, EDAS (JS‐SO), EHSB (JS‐OH‐SO), ETAC (JN) and EDHB (JS‐OH), in monovalent (NaCl) and divalent (CaCl2) salts. This is of great significance for the application of high‐salinity formation water to directly prepare fracturing fluids. The results showed that in high‐salinity aqueous solutions, both zwitterionic surfactants and cationic surfactants can exhibit extremely strong salt tolerance. The addition of the counter ion salt can destroy the internal salt, thus increasing water solubility of zwitterionic surfactants. Cationic surfactants have strong water solubility, and the counter ion Cl− will weaken the electrostatic shielding effect between the head groups. Surfactants can still maintain excellent network structures under high‐salinity conditions. This is mainly owing to the extreme insensitivity of zwitterionic surfactants to salts and the large initial head group area of cationic surfactants. In actual applications, the formation water from the Tahe Oilfield was used directly to prepare the fracturing fluids. Testing the rheological properties of fracturing fluid systems found that adding a small amount of hydrophobic associating polymers can increase the temperature resistance from 100 °C to 140 °C, and the final viscosity can be maintained above 30 mPa S. At the same time, they all showed excellent proppant suspension properties and extremely low core damage rates. The results indicated that even in high‐salinity formation water and high‐temperature formation, these fracturing fluid systems still have good performances, extremely low damage and meet fracturing fluid industry standards.

MPEG-carboxymethyl astaxanthin monoester: A novel hydrophilic astaxanthin with increased water solubility and bioavailability

To develop hydrophilic astaxanthin with significantly enhanced water solubility, an optimized one-step synthesis method was developed by heating free astaxanthin (F-Asta) and mPEG-carboxymethyl (mPEG-CM) in dichloromethane (27 °C) with two catalysts, yielding 61.38 ± 2.16% of mPEG-carboxymethyl astaxanthin monoester (mPC-Asta) in 12 h mPC-Asta showed a characteristic wavelength absorption at 441 nm with high dispersibility (206 mg mL−1) in water. The particle size of mPC-Asta nanomicelles was in the range of 10–30 nm. Experiments on storage stability indicated best maintenance of mPC-Asta nanomicelles at 4 °C, pH 5, in the dark and in the presence of nitrogen. The AUC0-t of Asta in the serum of mice after gavage of mPC-Asta nanomicelles was 9.05 ± 0.69 h μg·mL−1, which was significantly higher (four-fold) than that of F-Asta. The results show that mPC-Asta greatly enhances water solubility and bioavailability of astaxanthin.

Examination of dissolution ratio of β-carotene in water for practical application of β-carotene amorphous solid dispersion.

β-Carotene (BC) has an antioxidant effect that removes active oxygen in vivo and can reduce the risk of developing various diseases, but it is almost insoluble in water. Therefore, to develop highly effective BC functional food products, it is essential to increase its water solubility, which in turn can improve its absolute bioavailability. Recently, a BC amorphous solid dispersion (BC-SD) prepared using hot melt extruder technology had increased water solubility and improved absorption from the gastrointestinal tract. However, only a part of the BC in BC-SD could be dissolved in water. In this study, we evaluated whether the dissolution ratio of BC in water could be improved by examining the mixing ratio of BC and base materials in BC-SD. Results showed that by reducing the mixing ratio of BC to the base materials, the dissolution ratio of BC in water increased. It was also found that when BC-SD, which has the highest dissolution ratio, was intragastrically administered to rats, its absolute bioavailability was most increased. These results are useful findings that may help in reducing the costs associated with the BC-SD manufacturing process and will be an important part of our strategy for practical use in the future.

Development of Self-Nanoemulsifying Drug Delivery Systems Containing 4-Allylpyrocatechol for Treatment of Oral Infections Caused by Candida albicans.

Clinical use of 4-Allylpyrocatechol (APC), a potential antifungal agent from Piper betle, is limited because of its low water solubility. The current study explores the development of the self-nanoemulsifying drug delivery system (SNEDDS) containing APC (APC-SNEDDS) to enhance APC solubility. Results demonstrated that excipient type and concentration played an important role in the solubility of APC in the obtained SNEEDS. SNEDDS, comprising 20% Miglyol 812N, 30% Maisine 35-1, 40% Kolliphor RH40, and 10% absolute ethanol, provided the highest loading capacity and significantly increased water solubility of APC. Oil-in-water nanoemulsions (NE) with droplet sizes of less than 40 nm and a narrow size distribution were obtained after dispersing this APC-SNEDDS in water. The droplets had a negative zeta potential between −10 and −20 mV. The release kinetics of APC from APC-SNEDDS followed the Higuchi model. The NE containing 1.6 mg APC/mL had effective activity against Candida albicans with dose-dependent killing kinetics and was nontoxic to normal cells. The antifungal potential was similar to that of 1 mg nystatin/mL. These findings suggest that APC-SNEDDS are a useful system to enhance the apparent water solubility of APC and are a promising system for clinical treatment of oral infection caused by C. albicans.

Efficacy of Novel Formulations of Ivermectin and Albendazole in Parasitic Infections of Sheep in the Altai Mountains of Russia.

Background:Parasitic infections are widespread in sheep farms of the Russian Federation, including Siberia. The infection of sheep with helminths and parasitic arthropods with a range of 70% to 100% in different regions, contributes to a decrease in the productivity and quality of products, and even death of animals. This study aimed to formulate drugs with pronounced parasiticidal effects based on ivermectin and albendazole, widely used to treat animal entomoses and helminth infections.Methods:New formulations in the form of solid dispersed compositions were prepared by mechanochemical modification of ivermectin and albendazole using arabinogalactan polysaccharide. The efficacy of preparations on gastrointestinal strongylosis and monieziosis, and melophagosis of sheep was determined by parasitological examination and analysis of feces and urine.Results:The new formulations demonstrated increased solubility and parasiticidal activity due to the formation of inclusion complexes when interact with water. The maximum efficacy values (> 95% efficiency) against intestinal Strongylida and Moniezia expansa, and ectoparasitic Melophagus ovinus were seen in doses lower than the recommended doses of the starting drugs.Conclusion:The increased parasiticidal activity of innovative compositions can be explained by increased water solubility and bioavailability of the preparations, due to formation of inclusion complexes. The results of this study suggests the possibility of a significant reduction in the dosages of composed substances without losing their parasiticidal activity.

Gamma radiation application to rice: Reduced glycemic index in relation to modified carbohydrate observed in FTIR spectra

This study was conducted with a popular, low price Bangladesh rice variety BRRI Dhan 29 with a view to possible carbohydrate modification targeting lower glycemic index using gamma radiation application. Irradiation process (5 and 10 ​kGy ​at a dose rate of 9.74kGy/h) altered amylose content, amylose/amylopectin ratio, swelling power, and solubility index. FTIR spectroscopy confirmed the changed molecular structures due to radiation application. Treatment with a dose of 5 and 10kGy caused increased amylose and amylose/amylopectin ratio significantly (p ​< ​0.02). The highest amylose content was found in 10 ​kGy irradiated rice (30.20%) compared to unirradiated one (17.27%). Gamma radiation caused decreased swelling and increased water solubility in rice powder. These features of carbohydrate amendment in irradiated rice lead to reduced glycemic index as investigated with the in vivo experiments. Therefore, this study suggests gamma-irradiated rice (10kGy) is beneficial for diabetic subjects keeping lower blood glucose levels.

An environmentally safe formulation with enhanced solubility and fungicidal activity: Self-assembly and characterization of Difenoconazole-β-CD inclusion complex

Since pesticides have the disadvantages of low utilization rate and pollution to the surrounding environment, it is necessary to consider the development of new pesticide formulations. Difenoconazole (DZ), a common fungicide with poor water solubility, needs to be mixed with a large number of additives during use, which results in excessive use of organic solvents and pesticide residues. In this study, inclusion complex of beta-cyclodextrin (β-CD) and DZ was synthesized by ultrasonic method and was then aim to enhance the water solubility and its antifungal activity against Gibberella sp. of DZ. X-ray diffraction (XRD), nuclear magnetic resonance (1H NMR) analysis and molecular modeling techniques were applied to characterized the formation of DZ/β-CD inclusion complex, the DZ:β-CD stoichiometric ratio of the prepared inclusion complex was calculated in accordance with the result of 1H NMR. Increased water solubility of inclusion complex was illustrated by phase solubility studies. The inclusion complex showed a more significant fungicidal effect against Gibberella sp. than original DZ in the fungicidal effect assay. The inclusion complexation of β-CD on DZ was a new pesticide formulation and provided new development ideas for the application of DZ in agriculture.

Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol.

Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

Janus Dendrimers to Assess the Anti-HCV Activity of Molecules in Cell-Assays.

The use of nanocarriers has been revealed as a valid strategy to facilitate drug bioavailability, and this allows for expanding the drug libraries for the treatment of certain diseases such as viral diseases. In the case of Hepatitis C, the compounds iopanoic acid and 3,3′,5-triiodothyroacetic acid (or tiratricol) were identified in a primary screening as bioactive allosteric inhibitors of viral NS3 protease, but they did not exhibit accurate activity inhibiting viral replication in cell-based assays. In this work, dendritic nanocarriers are proposed due to their unique properties as drug delivery systems to rescue the bioactivity of these two drugs. Specifically, four different amphiphilic Janus dendrimers synthesized by combining 2,2′-bis(hydroxymethyl)propionic acid (bis-MPA) and 2,2′-bis(glyciloxy)propionic acid (bis-GMPA) functionalized with either hydrophilic or lipophilic moieties at their periphery were used to entrap iopanoic acid and tiratricol. Interestingly, differences were found in the loading efficiencies depending on the dendrimer design, which also led to morphological changes of the resulting dendrimer aggregates. The most remarkable results consist of the increased water solubility of the bioactive compounds within the dendrimers and the improved antiviral activity of some of the dendrimer/drug aggregates, considerably improving antiviral activity in comparison to the free drugs. Moreover, imaging studies have been developed in order to elucidate the mechanism of cellular internalization.

Modification of Apple Pomace by Extrusion Processing: Studies on the Composition, Polymer Structures, and Functional Properties.

By-products of fruit and vegetable processing are an inexpensive and sustainable source of dietary fiber, potentially offering valuable functional properties such as water binding and thickening. Due to these favorable properties, they can be utilized to reformulate widely-consumed foods, e.g., bakery products or beverages. In this study, apple pomace was used as a model system to study whether extrusion technology affects food by-product functionality and thus has the potential to broaden the application of by-products in foods. The effect of the process parameters and the extent of thermo-mechanical treatment on the structural and functional properties of apple pomace were analyzed after extrusion trials using various screw speeds, water contents, and barrel temperatures. Compared to the raw material, apple pomace extruded at Tbarrel = 100 °C, n = 700 min−1 and mH2O = 17% showed an increased water solubility up to 33%. The water absorption increased from 5 to 19 Pa·s and the paste viscosity from 5 to 339 Pa·s by extrusion processing. Analyses of dietary fiber contents and fiber polysaccharide structures revealed that thermo-mechanical stress (n = 700 min−1, mH2O = 22%) increased the content of soluble dietary fiber from 12.5 to 16.7 g/100 g dry matter, and that the harshest conditions even enabled the formation of low-molecular-weight dietary fiber. Arabinans (as neutral rhamnogalacturonan I side chains) appeared to be most sensitive to thermo-mechanical stress, whereas xylans (i.e., a group of minor polysaccharides) were an example of a more stable fiber polysaccharide. Also, the degree of methylation of the pectic polysaccharides was strongly reduced from 50% to 15% when thermo-mechanical stress was applied. Imaging and pore size analysis showed that extrusion processing could disrupt the rigid cell wall macromolecular structure.

Water-Soluble Substances of Arglabin

The article discusses the results of a study of the water solubility of natural sesquiterpene lactone arglabin, in particular, its ability to complex formation with complexing agents polyvinylpyrrolidone, the disodium salt of glycyrrhizic acid, magnesium carbonate. Mechanocomposites with polyvinylpyrrolidone and disodium salt of glycyrrhizic acid, which have increased water solubility, were obtained by the method of mechanochemical treatment of arglabin native. At the same time, the best result of dissolution in water is achieved by a two-hour treatment with polyvinylpyrrolidone and with disodium salt of glycyrrhizic acid. The water solubility of complex compounds of arglabin with polyvinylpyrrolidone increases by 4.61 times, and with disodium salt of glycyrrhizic acid by 4.42 times.

Discovery of heterocycle-containing α-naphthoflavone derivatives as water-soluble, highly potent and selective CYP1B1 inhibitors

Cytochrome P450 1B1 (CYP1B1) has been well validated as an attractive target for cancer prevention and drug resistance reversal. In continuation of our interest in this area, herein, a set of forty-six 6,7,10-trimethoxy-α-naphthoflavone derivatives varying in B ring was synthesized and screened against CYP1 enzymes, leading to the identification of fluorine-containing compound 15i as the most potent and selective CYP1B1 inhibitor (IC50 value of 0.07nM), being 84-fold more potent than that of the template molecule ANF. Alternatively, the amino-substituted derivative 13h not only possessed a potent inhibitory effect on CYP1B1 (IC50 value of 0.98nM), but also had a substantially increased water solubility as compared with the lead ANF (311μg/mL for 13h and <5μg/mL for ANF). The current study expanded the structural diversity of CYP1B1 inhibitors, and compound 13h could be considered as a promising starting point with great potential for further studies.