3‐Heterocycle‐Phenyl N‐Alkylcarbamates as FAAH Inhibitors: Design,Synthesis and 3D‐QSAR Studies

Carbamates are a well‐established class of fatty acid amide hydrolase (FAAH) inhibitors. Here we describe the synthesis of meta‐substituted phenolic N‐alkyl/aryl carbamates and their in vitro FAAH inhibitory activities. The most potent compound, 3‐(oxazol‐2yl)phenyl cyclohexylcarbamate ( 2 a ), inhibited FAAH with a sub‐nanomolar IC₅₀ value (IC₅₀=0.74 nM ). Additionally, we developed and validated three‐dimensional quantitative structure–activity relationships (QSAR) models of FAAH inhibition combining the newly disclosed carbamates with our previously published inhibitors to give a total set of 99 compounds. Prior to 3D‐QSAR modeling, the degree of correlation between FAAH inhibition and in silico reactivity was also established. Both 3D‐QSAR methods used, CoMSIA and GRID/GOLPE, produced statistically significant models with coefficient of correlation for external prediction (R²_PRED) values of 0.732 and 0.760, respectively. These models could be of high value in further FAAH inhibitor design.     

Water Activity and Temperature Effects on Fungal Growth and Ochratoxin A Production by Ochratoxigenic Aspergillus carbonarius Isolated from Tunisian Grapes

ABSTRACT: This study investigated the effects of temperature (15 to 37 °C) and water activity (0.90 to 0.99) on the growth and production of ochratoxin A (OTA) by Aspergillus carbonarius cultured on synthetic nutrient medium (SNM) after 5 and 10 d of incubation. Total of 8 ochratoxigenic A. carbonarius, isolated from vineyards located in different regions of Tunisia, were used. Growth data were modeled by the flexible model of Baranyi and growth rates at each set of conditions were obtained. For both growth and OTA production, optimal water activity was 0.99; however, optimal temperature varied. The optimal temperature for growth was 30 °C. At 37 °C, the growth rate decreased significantly (P < 0.05). Maximum toxin production occurred at temperatures in the range of 15 to 25 °C with the optimum one depending on the isolate tested. Significant amounts of OTA were produced after only 5 d of incubation. Our results showed that A. carbonarius isolated from Tunisian grapes behave as those from European and Australian grapes, as reported in the literature, although some differences in trends for growth and OTA production were observed.     

Stability and Antimicrobial Activity of Allyl Isothiocyanate during Long-Term Storage in an Oil-in-Water Emulsion

Abstract: This study investigated the stability and antimicrobial activity of allyl isothiocyanate (AITC) in medium chain triglyceride (MCT) or soybean oil (SBO) dispersed in an oil-in-water (o/w) system during long-term storage. Oil type, content, and oxidative stability affect the stability and antimicrobial activity of AITC during storage. High oil content is favorable for AITC stability in the emulsion. Notably, AITC with MCT is more stable than AITC with SBO with the same oil content. Consequently, AITC with MCT is more effective than AITC with SBO in inhibiting G(−) bacteria (E. coli O157:H7, Salmonella enterica, and Vibrio parahaemolyticus) and G(+) bacteria (Staphylococcus aureus and Listeria monocytogenes).     

磺化富马酸胺的合成及表面活性和杀虫性能研究

以硫酸、富马酸和-乙醇胺为原料合成磺化富马酸-乙醇胺，探求反应的最佳工艺条件，研究所得产品的杀虫性能，结果表明该产物具有良好的表面活性，对农业害虫具有良好的防治杀虫效果，可以成为农药化学新材料。     

Physicochemical characterisation,digestibility and anticonstipation activity of some high‐resistant untraditional starches from zingiberaceae plants

To find new starch sources with particular characteristics, five untraditional starches from zingiberaceae plants were studied about their physicochemical properties, digestibility and anticonstipation activity and compared with starches from traditional sources (potato and corn). All the five starches presented the shape of triangular, with visible thin sheet, which were significantly different from conventional sources. The crystal type of these five starches was B‐type pattern. Swelling power at 75 °C was negatively correlated with crystallinity. There was no significant difference in amylose content between starches from rhizome and tuber of Curcuma phaeocaulis Val., while they displayed significant variability in RS content. Starches from rhizome of Curcuma kwangsiensis, Curcuma wenyujin, Curcuma phaeocaulis Val. and Curcuma longa L. possessed much higher resistant starch content (range from 87.06% to 95.40%) and could better prevent constipation than potato and corn starches, which made them potential for managing diabetes and improving defecation conditions.     

The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH‐like 2‐Heptyl‐3‐hydroxy‐4(1H)‐quinolone (PQS) Biosynthesis Enzyme PqsBC

Pseudomonas aeruginosa is a bacterial pathogen that causes life‐threatening infections in immunocompromised patients. It produces a large armory of saturated and mono‐unsaturated 2‐alkyl‐4(1H)‐quinolones (AQs) and AQ N‐oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β‐ketoacyl‐acyl‐carrier protein synthase III (FabH)‐like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2‐heptyl‐4(1H)‐quinolone (HHQ), by condensing octanoyl‐coenzyme A (CoA) with 2‐aminobenzoylacetate (2‐ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium‐chain acyl‐CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono‐unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl‐binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH‐enzymes, for which such structural transitions have been postulated but have never been observed.     

Enhanced antibacterial activity of tetramethylguanidinium-conjugated linear polyethylenimine polymers

In the present study, varying amounts of tetramethylguanidinium moiety have been conjugated to linear polyethylenimine to obtain linear polyethylenimine-tmg (LPTG) polymers. Incorporation of hydrophobic and highly basic moiety in the polymeric backbone resulted in the significant improvement in the antibacterial activity which was confirmed by zone of inhibition and MIC assays. Further, the results of transmission electron microscopy and confocal studies revealed that the projected LPTG polymers possessed higher antibacterial activity than the native polymer. In addition, these modified polyethylenimine (PEI) polymers were capable of reducing auric chloride into stable gold nanoparticles. These polyamine-stabilized gold nanoparticles can be used in various biomedical applications.     

Optimization of Hydrolysis Conditions for the Production of Antioxidant Peptides from Fish Gelatin Using Response Surface Methodology

Abstract: Fish skin gelatin was hydrolyzed with papain to produce antioxidant peptides. Response surface methodology (RSM) was applied to optimize the hydrolysis conditions (including enzyme to substrate ratio [E/S], hydrolysis time, and temperature). The highest degree of hydrolysis (DH) (50.1 ± 1.1%) was obtained at an E/S of 2% at 56.8 °C, 2.11 h, and was not significantly different from the predicted values within a 95% confidence interval. The highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) (96.8 ± 0.9%) and 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS^•+) (9.80 ± 0.11 mM Trolox [6-hydroxy-2,5,7,8-tetramethychroman-2-carboxylic acid]) radical-scavenging activities of fish gelatin hydrolyzates were obtained at an E/S of 3% at 52.1 °C, 2.65 h, and both DPPH and ABTS^•+ radical-scavenging activities were not significantly different from the predicted values 97.3% and 9.86 mM Trolox within the 95% confidence interval. Therefore, RSM is an efficient way to optimize fish gelatin hydrolysation and the resultant hydrolyzates show promise as antioxidant peptides. Practical Application: There is a growing interest in the use of fish gelatin as an alternative to mammalian gelatin. One potential use is as a source of widely acceptable functional compounds. In this study, a search for antioxidant peptides from fish gelatin prepared by an enzymatic method has been successfully done. This suggests that this is a practical way to obtain bioactive peptides.     

Evaluation of antioxidant and anti-initiating activities of crude polyphenolic extracts from seedless and seeded Indian grapes

The extracts of crude polyphenols (seeds, pulp + skin, whole) from four different cultivars of Indian grapes were used in this study. The total polyphenolic contents of grape polyphenolic extracts (GPEs) were determined and their in vitro antioxidant and anti-initiating activities evaluated. The total polyphenolic contents, expressed in terms of gallic acid/catechin/procyanidin B3 equivalents, were found to vary significantly. Antioxidant activity of GPEs, particularly the seedless variety, was evident from significant dose-dependent inhibition of lipid peroxidation and DPPH activity. GPEs and catechin inhibited the microsome-catalysed activity of cytochrome P450 isozymes (1A1, 1A2, 2B1) in a dose-dependent manner, by the decreased formation of resorufin. The inhibitory activity of GPEs on nitrite-mediated N-nitrosation of dimethylamine and N-methylaniline appears to correlate significantly with the total polyphenolic contents. Furthermore, six individual polyphenols present in GPEs were quantitated by HPLC, wherein procyanidin B3 was a major constituent.     

Antioxidant and anti‐acetylcholinesterase activities of anchovy (Coilia mystus) protein hydrolysates and their memory‐improving effects on scopolamine‐induced amnesia mice

Anchovy protein hydrolysates (APHs) were prepared through hydrolysis for 2, 4 or 8 h (APH‐2, APH‐4 and APH‐8, respectively). The chemical analyses, in vitro assessments [antioxidant activity and acetylcholinesterase (AchE) inhibitory activity] and in vivo mice tests were evaluated. Results revealed that APH‐8 exhibited the strongest reducing power and AchE inhibitory capacity (IC₅₀ = 159.76 ± 0.03 mg mL^?1), which may be due to its specific amino acid composition and newly formed peptides. In addition, AchE inhibitory kinetics of amino acids suggested that lysine was featured of both competitive and noncompetitive inhibitors. Furthermore, the results of in vivo study showed that all APHs exhibited memory‐improving action on scopolamine‐induced amnesia mice especially, APH‐8, indicating that anchovy protein is a potential source for health‐promoting peptides.