Effects of different extraction methods on volatile profiles of flaxseed oils.

To investigate the effects of different extraction methods on volatile compounds in flaxseed oil (FSO), we first carried out solvent extraction, cold pressing, and hot pressing treatments of flaxseed [Linum usitatissimum (L.)], then applied the headspace-gas chromatography-ion mobility spectrometry technology to identify the volatile substance compositions, and established flavor fingerprints of solvent-extracted FSO, cold-pressed FSO, and hot-pressed FSO. In total, 81 volatile compounds were detected, including 27 aldehydes, 14 alcohols, 13 ketones, 9 heterocycles, 8 esters, 5 acids, 4 hydrocarbons, and 1 sulfur compound (dimethyl disulfide). Extraction methods had a great influence on the volatile profile of FSO. Solvent-extracted FSO had more sweet, mild, floral, and sour volatile profiles, cold-pressed FSO had stronger volatile profiles of winey, spicy, and fatty, and hot-pressed FSO had green, grass, and plastic volatile profiles. Principal component analysis and Euclidean distance demonstrated that the volatile compounds of three FSO samples could be clearly distinguished. Of note, the cold-pressed FSO and hot-pressed FSO had similar volatile profiles, and they were different from solvent-extracted FSO. This study could provide some guidance for improving the flavor quality of FSO and selecting the proper extraction method for FSO productions. PRACTICAL APPLICATION: Practical Application: This study shows extraction methods significantly affect the formation of aroma characteristics in flaxseed oil (FSO), and it provides theoretical guidance for production to use the appropriate extraction methods for high-quality FSO.

Impact of de-branched starch molecules and fatty acid complexes on the attenuation of ageing-induced cognitive impairment.

BACKGROUND: Ageing and associated cognitive impairments are becoming serious issues around the world. In this study, the physiological properties of three kinds of complexes of fatty acid (capric, stearic and oleic acid, respectively) and de-branched starch molecules were investigated via a d-galactose-induced ageing model. This study revealed differences in the regulation of cognitive impairment and brain damage following intervention of different complexes, which might highlight a potent approach for the prevention of this chronic disease. RESULTS: Data indicated that three complexes improved response time and cognitive function and the bio-parameter markers associated with oxidative stress in ageing rats. Among them, the complexes prepared from de-branched starch-oleic acid showed a greater improvement compared to others. In addition, de-branched starch-capric acid complex showed a higher improvement in the morphology of colon cells and hippocampal neuronal cells. The consumption of de-branched starch-capric acid and -oleic acid complexes generated more short-chain fatty acids in the gut. More importantly, the complexation of de-branched starch with either caprate or stearate enhanced gut Akkermansia. Therefore, it was proposed that the richness in Akkermansia and gut metabolites might be associated with reduced damage of the hippocampal neuronal cells induced by the ageing progress. Moreover, the AMPK (AMP-activated protein kinase) pathway was activated in liver in de-branched starch-capric acid complex diet. In summary, de-branched starch-capric acid complex exhibited a greater effect on the attenuation of ageing-induced cognitive impairment. CONCLUSION: This study might highlight a new approach for intervening in the cognitive impairment during the ageing progress via a food supply. © 2023 Society of Chemical Industry.

Insights on the binding mechanism between specified aldehydes and flaxseed protein using multispectral image and molecular docking.

The binding and release behavior of flaxseed proteins to aldehydes is significant for the sensory properties of flaxseed foods. The key aldehydes of flaxseed were selected by headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and odor activity value (OAV) method, and the interaction between flaxseed protein and flaxseed protein was investigated by multispectral, molecular docking, molecular dynamics simulation, and particle size techniques. The results showed that 2,4-decadienal presented a higher binding capability and a higher Stern-Volmer constant with flaxseed protein than pentanal, benzaldehyde, and decanal. Thermodynamic analysis revealed that hydrogen bonding and hydrophobic interactions were the main forces. Aldehydes contributed to a certain reduction in radius of gyration (Rg) value and α-helix content of flaxseed protein. In addition, the results of particle size showed that aldehydes caused the proteins to aggregate toward larger particles. This study could provide new insights into the interactions between flaxseed food and flavor.

Microencapsulation of tomato seed oil using phlorotannins-adducted pea protein isolate-chitosan and pea protein isolate-chitosan complex coacervates.

Pea protein isolates (PPI)/phlorotannins (PT)/chitosan (CS) ternary complex and PPI/CS binary complex were synthesized to prepare tomato seed oil (TSO) microcapsules. The concentration of PT was determined to be 0.025% (w/w) based on the solubility, emulsification, and UV-visible spectrum of PPI-PT complex. Subsequently, the optimal pHs associated with the formation of PPI/CS and PPI-PT/CS complex coacervates were determined to be pH 6.6 and 6.1, while the optimal ratios were 9:1 and 6:1, respectively. The coacervate microcapsules were successfully produced by freeze-dried method and those formulated with PPI-PT/CS displayed significantly lower surface oil content (14.57 ± 0.22%), higher encapsulation efficiency (70.54 ± 0.13%), lower particle size (5.97 ± 0.16 µm), and PDI (0.25 ± 0.02) than PPI/CS. The microcapsules were characterized by scanning electron microscopy and Fourier Transform infrared spectroscopy. Furthermore, the encapsulated TSO exhibited enhanced thermal and oxidative stability than that of free oil, along with microcapsules fabricated with PPI-PT/CS ternary complex showed better protection than that of free PT. Overall, PPI-PT/CS complex as an effective wall material in delivery system presented great potential.

Synthesis and evaluation of hydrazinyl-containing pyrrolo[2,3-d]pyrimidine series as potent, selective and oral JAK1 inhibitors for the treatment of rheumatoid arthritis.

Selective inhibition of JAK kinases within the JAK family has been a desired goal of research in order to maximize efficacy while reducing undesired off target effect. Aiming to minimize adverse effects such as anemia, a promising new class of pyrrolo[2,3-d]pyrimidine series containing a hydrazinyl moiety were synthesized and profiled. Among them compound 8m and 8o showed the best enzymatic activity against JAK1 with IC50 value of 0.16 nM and 0.3 nM respectively, and with selectivity over JAK2 by 40.6 and 10 folds respectively. In addition, 8o had an improved PK profile and demonstrated better in vivo efficacy than Tofacitinib in CIA model.

Effect of roasting temperature and time on volatile compounds, total tocopherols, and fatty acids of flaxseed oil.

Roasting affects the physicochemical and nutritional qualities of flaxseed oil (FSO). The FSO samples were extracted from the roasting flaxseeds at 10-, 20-, and 30-min points and at different temperatures (140°C, 160°C, and 180°C). A total of 61 volatile compounds were identified, and the quantity of the volatile compounds increased significantly (p < 0.05) after roasting. The maximum aldehyde (25.83%) and heterocyclic content (29.26%) was obtained from the samples roasted at 200°C for 20 and 30 min, respectively. The predominant fatty acid in FSO samples was linolenic acid (46.01%-49.35%), which changed dynamically during roasting. The loss of α-, γ-, and δ-tocopherol after roasting was 28.73, 109.78, and 6.67 mg/100 g, respectively. The principal component analysis and hierarchical cluster analysis results showed good discrimination of the different FSO samples into three groups, which were mainly related to the roasting time. Therefore, it can be concluded that roasting time has a stronger effect on the volatile composition of FSO than the temperature during the roasting process. This work provides a basis for improving the aroma of FSO. PRACTICAL APPLICATION: The roasting process is used to extract flaxseed oil (FSO) from flaxseeds. Studying the physicochemical properties and quality characteristics of FSO under diverse roasting conditions is an important step in producing FSO in the food industry, which can give precise instructions to produce flaxseed oil in factories. The results of this study document the volatile constituents generated in FSO samples extracted from flaxseeds during roasting, which may help manufacturers, who are trying to develop natural and artificial FSO flavors.

Isolation and pathogenic characterization of duck adenovirus 3 mutant circulating in China.

Duck adenoviruses (DAdVs) include serotype 1 (DAdV-1) in the genus Atadenovirus and serotypes 2-4 (DAdV-2, 3, and 4) in the genus Aviadenovirus. DAdV-3 was initially isolated from Chinese Muscovy ducks in 2014, whereby the infected ducks exhibited yellowing and hemorrhaging in the liver, along with slight pericardial effusion, swelling, and hemorrhaging in the kidneys. In recent years, duck adenovirus infections have appeared in Muscovy duck farms in Fujian, Zhejiang, Anhui, Guangdong, and other places in China. They have an incidence rate of 40 to 55% and a mortality rate of 35 to 43%, resulting in great losses to the duck breeding industry. In this study, 7 DAdV-3 strains, designated as TZ193, FJPT20161124, GX20170519, FJZZ, GDMM, AHAQ, and GDHS were isolated from Muscovy ducks in different provinces of China during 2016-2019, and their complete genomics were sequenced. Their genomes all exhibited significant deletions in ORF67, which also had G to A transitions at the 41st and 977th nt positions, resulting in a stop codon. The pathogenicity of TZ193, a novel isolate of DAdV-3, was investigated in Muscovy ducks. TZ193 caused characteristic lesions of swelling as well as hemorrhagic liver and kidney in the infected ducklings. Moreover, the mortality rate of TZ193 in 5-day-old domestic ducks was 100%. Our data provide concrete evidence for the identification of the DAdV-3 novel variant mutant in China, which effects increased mortality in ducks. This highlights the necessity for monitoring the specific molecular epidemiology of novel DAdV-3 mutants and the development of new vaccines in the future.

Roasting treatments affect oil extraction rate, fatty acids, oxidative stability, antioxidant activity, and flavor of walnut oil.

Introduction: The quality of pressed walnut oil can be improved by moderate roasting treatment. Methods: This study compared physicochemical characteristics and antioxidant ability of walnut oils pressed from differently roasted pretreated walnuts, analyzed the correlation among these indicators by using Pearson correlation coefficient and correlation coefficient heatmap, and evaluated the volatile organic compounds (VOCs) of walnut oil under optimal pretreatment roasting conditions using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Results: Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were able to remarkably distinguish walnut oil produced by different roasting processes. In addition, correlation analysis showed that there was a significant impact among indicators. There were 73 VOCs were identified in the optimum roasted treated walnut oil, consisting of 30 aldehydes, 13 alcohols, 11 ketones, 10 esters, 5 acids, 2 oxygen-containing heterocycles, 1 nitrogen-containing heterocycle and 1 other compound. GC-IMS results showed that aldehydes contributed significantly to the volatile flavor profile of walnut oil, especially (E)-2-heptenal, (E)-2-pentenal and hexenal. Discussion: The properties of walnut oil based on varying roasting pretreatment of walnut kernels were significantly differentiated. Roasting at 120°C for 20 min is a suitable pretreatment roasting condition for pressing walnut oil. Roasting at 120°C for 20 min is a suitable pretreatment roasting condition for pressing walnut oil.

Preparation and physicochemical stability of tomato seed oil microemulsions.

In this study, microemulsions were fabricated using tomato seed oil, water, Tween 80 and citric acid, and then the physicochemical characteristics and the influence of environmental stress were investigated. The physicochemical properties of the microemulsions were evaluated by transmission electron microscopy (TEM), mean particle diameter, polydispersity index (PDI) and conductivity. The phase diagrams of tomato seed oil/Tween 80/citric acid/water microemulsions were constructed under different pHs and ionic strengths. Storage stability of the systems was investigated at 4, 37 and 65°C, and changes in turbidity and lipid oxidation products were monitored. Nano-size zeta potential analyzer results demonstrated that the mean particle diameter and polydispersity index of tomato seed oil microemulsions were 14 nm and 0.014. The transition from W/O to O/W could be detected from electrical conductivity and viscosity data with the increasing of water content. The results showed that the microemulsion areas decreased with increasing pH and NaCl concentrations. What is more, the study proved that tomato seed oil microemulsions exhibited a good storage stability. PRACTICAL APPLICATION: In this study, the preparation of tomato seed oil microemulsion can not only make full use of the nutritional value of tomato seed oil, but also ensure the effective protection of the nutrients contained in it, and improve the problem of adding difficult. By using microemulsion as delivery carrier of tomato seed oil, the application of tomato seed oil in food, cosmetics and other fields could be enhanced. Therefore, the preparation of tomato seed oil microemulsion provides a theoretical basis for production practice.

Comparison of the effect of extraction methods on the quality of green coffee oil from Arabica coffee beans: Lipid yield, fatty acid composition, bioactive components, and antioxidant activity.

In this study, ultrasonic/microwave-assisted extraction (UMAE), microwave-assisted extraction (UAE), ultrasound-assisted extraction (UAE), and pressurized liquid extraction (PLE) were applied to extract green coffee oil (GCO), and the physicochemical indexes, fatty acids, tocopherols, diterpenes, and total phenols as well as antioxidant activity of GCO were investigated and compared. The results indicated that the extraction yield of UMAE was the highest (10.58 ± 0.32%), while that of PLE was the lowest (6.34 ± 0.65%), and linoleic acid and palmitic acid were the major fatty acids in the GCO, ranging from 40.67% to 43.77% and 36.57% to 38.71%, respectively. A large proportion of fatty acids and phytosterols were not significantly influenced by the four extraction techniques. However, tocopherols, diterpenes, total phenols, and the free radical scavenging activity were significantly different among these four GCOs. Moreover, structural changes in the coffee residues were explored by scanning electron microscopy and Fourier transform infrared spectroscopy. Overall, the high antioxidant activity of GCO demonstrated that it can be used as a highly economical natural product in the food and agricultural industries.

Coinfection of parvovirus and astrovirus in gout-affected goslings.

Outbreaks of gosling gout have occurred in China since 2017 and caused a considerable economic impact on the poultry industry. While gosling astrovirus (GoAstV) is believed to be the main causal pathogen of gout, the full-blown disease of gout cannot be well reproduced by infecting the goslings with GoAstV, suggesting the possibility of other infectious agents being involved with the development of gosling gout. To assess other possible infectious agents, we collected tissues from gout-affected goslings in 12 goose farms in China, followed by PCR detection of GoAstV, goose reovirus (GRV), goose parvovirus (GPV), fowl adenovirus (FAdV), goose circovirus (GcoV), Tembusu virus (TMUV) and goose haemorrhagic polyomavirus (GHPV). Our data showed that all gout-affected goslings carried both of GoAstV and GPV determined by PCRs, and this was further confirmed by fluorescence multiplex immunohistochemical staining, and phylogenetic analysis of ORF2 gene of GoAstV and VP3 gene of GPV. In addition to the haemorrhage in the kidney, liver, spleen and lung of the gout-affected goslings, histological examinations showed also extensive infiltration of heterophil myelocytes in the kidney, liver, spleen, bursa of Fabricius, thymus, lungs and pancreas. Our findings strongly suggest that coinfection of GoAstV and GPV increases the severity of gout. While this is the first study to report GPV in gout-affected goslings, further studies including infection model are warranted to investigate the role of GPV and its coinfection with GoAstV in the development of gosling gout.

Co-expression of surfactant protein A and chicken lung lectin in chicken respiratory system.

Chicken surfactant protein A (cSP-A) and chicken lung lectin (cLL) are C-type lectins that play important roles in pulmonary host defense responses. Herein, we explored the localization of cSP-A and cLL in the chicken respiratory system. Six tissues from 30-days-old SPF chickens were used to quantify the expression of cSP-A and cLL using the quantitative real-time reverse transcriptional polymerase chain reaction (qRT-PCR) and fluorescence multiplex immunohistochemistry staining (fluorescence mIHC staining). Results showed that cSP-A and cLL mRNA were highly expressed in lungs compared to other tissues. cSP-A mRNA expression levels in all tissues were higher compared with cLL expression levels as analyzed using qRT-PCR. Fluorescence mIHC co-expression of cSP-A and cLL were mainly detected in lung parabronchial epithelia, and mucosal epithelia of larynx, trachea, syrinx, bronchus and air sac, with cSP-A showing a stronger positive staining compared with cLL. cLL is expressed on both mucosal surfaces, some individual lung epithelial cells and cartilage cells, while cSP-A is mainly restricted to mucosal surfaces of the respiratory tract. These histological findings may be useful for understanding the biological significance of this pulmonary lectins in future studies.

Comprehensive analysis of volatile compounds in cold-pressed safflower seed oil from Xinjiang, China.

Three varieties of safflower seed oil (SSO) from Xinjiang Autonomous Region, China, were analyzed by headspace solid-phase micro-extraction gas chromatography coupled with mass spectrometry (HS-SPME-GC-MS) to reveal volatile components. Overall, 67 volatile components were determined and four compounds including isoamyl alcohol, caproic acid, n-pentanal, and heptanal were newly identified in SSO as aroma-active components. Meanwhile, 16 compounds were selected by relative odor activity value (ROAV) to evaluate contributions of single compounds to the overall odor (ROAV > 1), in which nonanal, (Z)-6-nonenal, and (E)-2,4-decadienal were the top three contributed substances (ROAV > 70). The sensory panel was described as eight definition terms (grassy, fruity, almond, mushroom, fatty, sweet, paddy, and overall fragrance). Principal component analysis (PCA) revealed a significant separation of three cultivars with the first principal component (PC-1) and the second principal component (PC-2) expressing 73.9% and 23.1%, respectively. Both PCA and ROAV allowed identifying the compounds positively correlated to sensory evaluation.

Characterization of the Aroma-Active Compounds in Commercial Fragrant Rapeseed Oils via Monolithic Material Sorptive Extraction.

Commercial fragrant rapeseed oil (CFRO), from roasted and hot-pressed seeds, is enjoyed in China for its unique aroma. However, the characteristic of aroma-active compounds in CFRO is still unclear. In this study, a new odor monolithic material sorptive extraction method was established to trap volatiles from rapeseed oil. Thirty CFROs were investigated using this method coupled with gas chromatography-mass spectrometry. A total of 29 volatile compounds were identified by gas chromatography-olfactometry including pyrazines, alcohols, aldehydes, ketones, and sulfur compounds. Further, 2,5-dimethylpyrazine (peanut-like), 3-ethyl-2,5-dimethylpyrazine (roasted nut-like), dimethyl trisulfide (cabbage-like), 4-isothiocyanato-1-butene (pungent and pickle-like), butyrolactone (caramel-like), and benzyl nitrile (pungent and sulfur-like) are affirmed as the key odorants for the overall aroma of CFRO, owing to their odor activity values ≥1. This work provides a new insight on acquiring aroma-active compounds from rapeseed oil in a more time-effective process compared to conventional methods. Futhermore, this novel approach is applicable in the field of food flavor.

Systematic investigation of the mechanism of Cichorium glandulosum on type 2 diabetes mellitus accompanied with non-alcoholic fatty liver rats.

Cichorium glandulosum(CG) can treat various diseases with multiple targets effectively. It has been widely used in folk medicine to treat nonalcoholic fatty liver disease (NAFLD) as well as type 2 diabetes mellitus (T2DM). However, the active compounds and underlying mechanisms of CG on T2DM accompanied with NAFLD (T2DM-NAFLD) remain unclear. In this study, a systems pharmacology method was used to explain the pharmacology mechanism of CG for treatment of T2DM-NAFLD. Twenty four main compounds were detected by UPLC-Q-TOF-MS, of which 13 showed favorable pharmacokinetic profiles. We demonstrated with target fishing and pathway analysis that CG has protective effects on T2DM-NAFLD, probably through the regulation of 88 targets and 86 pathways. Forty nine targets were related to T2DM, and 39 were related to NAFLD, while 27 targets, primarily involved in insulin resistance and inflammation were common to T2DM and NAFLD related pathways. A NF-κB signaling pathway was chosen to validate the impacts of CG on T2DM-NAFLD because CG can ameliorate T2DM-NAFLD by regulating the NF-κB signaling pathway according to animal experiments. These findings systematically interpreted the active compounds and mechanism of the efficiency of CG for treating T2DM-NAFLD. This study not only laid a basis for understanding the active compounds and action mechanism of CG, but also provides a reference for a study of the mechanism of a herbal medicine for the treatment of multiple diseases.

Structure activity relationship of pyridoxazinone substituted RHS analogs of oxabicyclooctane-linked 1,5-naphthyridinyl novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-6).

Oxabicyclooctane linked 1,5-naphthyridinyl-pyridoxazinones are novel broad-spectrum bacterial topoisomerase inhibitors (NBTIs) targeting bacterial DNA gyrase and topoisomerase IV at a site different than quinolones. Due to lack of cross-resistance to known antibiotics they present excellent opportunity to combat drug-resistant bacteria. A structure activity relationship of the pyridoxazinone moiety is described in this Letter. Chemical synthesis and activities of NBTIs with substitutions at C-3, C-4 and C-7 of the pyridoxazinone moiety with halogens, alkyl groups and methoxy group has been described. In addition, substitutions of the linker NH proton and its transformation into amide analogs of AM-8085 and AM-8191 have been reported. Fluoro, chloro, and methyl groups at C-3 of the pyridoxazinone moiety retained the potency and spectrum. In addition, a C-3 fluoro analog showed 4-fold better oral efficacy (ED50 3.9 mg/kg) as compared to the parent AM-8085 in a murine bacteremia model of infection of Staphylococcus aureus. Even modest polarity (e.g., methoxy) is not tolerated at C-3 of the pyridoxazinone unit. The basicity and NH group of the linker is important for the activity when CH2 is at the linker position-8. However, amides (with linker position-8 ketone) with a position-7 NH or N-methyl group retained potency and spectrum suggesting that neither basicity nor hydrogen-donor properties of the linker amide NH is essential for the activity. This would suggest likely an altered binding mode of the linker position-7,8 amide containing compounds. The amides showed highly improved hERG (functional IC50 >30 µM) profile.

Hydroxy tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of RHS moiety (Part-3).

Novel bacterial topoisomerase inhibitors (NBTIs) are a new class of broad-spectrum antibacterial agents targeting bacterial Gyrase A and ParC and have potential utility in combating antibiotic resistance. (R)-Hydroxy-1,5-naphthyridinone left-hand side (LHS) oxabicyclooctane linked pyridoxazinone right-hand side (RHS) containing NBTIs showed a potent Gram-positive antibacterial profile. SAR around the RHS moiety, including substitutions around pyridooxazinone, pyridodioxane, and phenyl propenoids has been described. A fluoro substituted pyridoxazinone showed an MIC against Staphylococcus aureus of 0.5 µg/mL with reduced functional hERG activity (IC50 333 µM) and good in vivo efficacy [ED90 12 mg/kg, intravenous (iv) and 15 mg/kg, oral (p.o.)]. A pyridodioxane-containing NBTI showed a S. aureus MIC of 0.5 µg/mL, significantly improved hERG IC50 764 µM and strong efficacy of 11 mg/kg (iv) and 5 mg/kg (p.o.). A phenyl propenoid series of compounds showed potent antibacterial activity, but also showed potent hERG binding activity. Many of the compounds in the hydroxy-tricyclic series showed strong activity against Acinetobacter baumannii, but reduced activity against Escherichia coli and Pseudomonas aeruginosa. Bicyclic heterocycles appeared to be the best RHS moiety for the hydroxy-tricyclic oxabicyclooctane linked NBTIs.

Structure activity relationship of substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-4).

Bacterial resistance is rapidly growing, necessitating the need to discover new agents. Novel bacterial topoisomerase inhibitors (NBTIs) are new class of broad-spectrum antibacterial agents targeting bacterial DNA gyrase and topoisomerase IV. This class of inhibitors binds to an alternative binding site relative to fluoroquinolones and shows no cross-resistance to quinolones. NBTIs consist of three structural motifs. A structure activity relationship of the left hand motif 1,5-naphthyridine of oxabicyclooctane-linked NBTIs is described. Fifty five compounds were evaluated against a panel of key Gram-positive and Gram-negative strains of bacteria, as well as for hERG activity and five compounds were tested for in vivo efficacy in murine model of Staphylococcus aureus infection. These studies suggest that only a narrow range (activating and deactivating) of substitutions at C-2 and C-7 are tolerated for optimal antibacterial activity and spectrum. An alkoxy (methoxy) and CN at C-2, and a halogen and hydroxyl at C-7, appeared to be preferred in this series. Substitutions on the other three carbons generally have detrimental effect on the activity. No clear hERG activity SAR emerged from these substitutions.

Tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of left-hand-side moiety (Part-2).

Novel bacterial topoisomerase inhibitors (NBTIs) represent a new class of broad-spectrum antibacterial agents targeting bacterial Gyrase A and ParC and have potential utility in combating antibiotic resistance. A series of novel oxabicyclooctane-linked NBTIs with new tricyclic-1,5-naphthyridinone left hand side moieties have been described. Compounds with a (R)-hydroxy-1,5-naphthyridinone moiety (7) showed potent antibacterial activity (e.g., Staphylococcus aureus MIC 0.25 µg/mL), acceptable Gram-positive and Gram-negative spectrum with rapidly bactericidal activity. The compound 7 showed intravenous and oral efficacy (ED50) at 3.2 and 27 mg/kg doses, respectively, in a murine model of bacteremia. Most importantly they showed significant attenuation of functional hERG activity (IC50 >170 µM). In general, lower logD attenuated hERG activity but also reduced Gram-negative activity. The co-crystal structure of a hydroxy-tricyclic NBTI bound to a DNA-gyrase complex exhibited a binding mode that show enantiomeric preference for R isomer and explains the activity and SAR. The discovery, synthesis, SAR and X-ray crystal structure of the left-hand-side tricyclic 1,5-naphthyridinone based oxabicyclooctane linked NBTIs are described.

Improvement of flavour quality and consumer acceptance during postharvest ripening in greenhouse peaches by carbon dioxide enrichment.

In this study we assessed the impact of carbon dioxide enrichment (CDE) on flavour quality development of peach fruit, using peach trees grown in a greenhouse with a carbon-dioxide-enriched atmosphere. Fruit sugar, organic acids, volatiles contents and consumer acceptability were investigated, focusing on the period of postharvest ripening. Higher levels of sucrose, lactones, norisoprenoids, and lower levels of malic acid were found in CDE-treated fruit than those in the control fruit grown under normal conditions. We also measured significantly elevated amounts of pyruvic acid, precursors of volatile compounds, linoleic acid and linolenic acid as a result of CDE. Additionally, CDE-treated fruit were relatively well accepted by consumers compared to the control fruit. These results suggested that CDE can markedly improve the flavour quality and consumer acceptance of greenhouse-grown peaches. The possible mechanism could be that CDE increased precursors available for the biosynthesis of flavour compounds through regulation of photosynthesis.