Synthesis and Evaluation of Bioactivity of 6-[(2-Pyridinyloxy)](Benzo)Imidazo[2,1-b][1,3]Thiazine Derivatives

A series of new 6-[(pyridine-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b]thiazines 4a-l and their benzoannelated derivatives 4m-r was synthesized by the reaction between 3-hydroxy(benzo)imidazo[2,1-b][1,3]thiazines and substituted 2-chloropyridines under the mild conditions with the yield 53-74 %. The structure of the target compound was proven by the results of 1H NMR, 13C NMR spectrometry, and LC-MS. In silico evaluation of these drug-like compounds proved that many of them comply with the Lipinski ‘rule of five’ and the Veber rule. Antibacterial, antifungal, and anti-inflammatory activity of all synthesized compounds were investigated in the in vitro and in vivo experiments. According to the bio screening results, the compounds 6-[(5-сhloropyridin-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4a, 6-[(3,5-dichloropyridin-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4e and 6-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}-2,3-diphenyl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4l proved antifungal activity against Candida albicans. On the other hand, 3-[(3,5-dichloropyridin-2-yl)oxy]-3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazine 4q proved the best antifungal activity against Aspergillus niger K 9 (MIC=15.62 µg/ml) and comparatively high antiedema activity against the carrageenan-induced edema of the hind paws of albino rats (the inflammation suppression index was 39.1 %).

NMR Metabolite Profiles of the Bivalve Mollusc Mytilus galloprovincialis Before and After Immune Stimulation With Vibrio splendidus

The hemolymph metabolome of Mytilus galloprovincialis injected with live Vibrio splendidus bacteria was analyzed by 1H-NMR spectrometry. Changes in spectral hemolymph profiles were already detected after mussel acclimation (3 days at 18 or 25 °C). A significant decrease of succinic acid was accompanied by an increase of most free amino acids, mytilitol, and, to a smaller degree, osmolytes. These metabolic changes are consistent with effective osmoregulation, and the restart of aerobic respiration after the functional anaerobiosis occurred during transport. The injection of Vibrio splendidus in mussels acclimated at 18°C caused a significant decrease of several amino acids, sugars, and unassigned chemical species, more pronounced at 24 than at 12 h postinjection. Correlation heatmaps indicated dynamic metabolic adjustments and the relevance of protein turnover in maintaining the homeostasis during the response to stressful stimuli. This study confirms NMR-based metabolomics as a feasible analytical approach complementary to other omics techniques in the investigation of the functional mussel responses to environmental challenges.

Recent Progress on Synthesis and Bio-activities of Tetrahydropyrimidine-2-one derivatives

This review covers up synthesis, characterization and Pharmacological activities of various derivatives of 1,2,3,4-Tetrahydropyrimidine-2-one, including recent mechanistic advances, new building blocks and new pharmacological disclosures. Tetrahydropyrimidines (THPs) are one of the most important systems among the heterocycles. These compounds reported to have less toxicity to human and animals. Various synthesis strategies have been reported for different derivatives of Tetrahydropyrimidines, mainly these involves Biginelli reaction (condensation) consisting of one pot synthesis of 1,2,3,4-Tetrahydropyrimidine derivatives using urea, β-keto ester and aldehyde. These derivatives also forms important part as intermediate in the manufacture of various Pharmaceuticals. Techniques such as infrared spectroscopy, liquid chromatography-mass spectrometry, 1H NMR and 13C NMR spectrometry along with single crystal X-ray diffraction has been reported for structural characterization of these derivatives. U.S. National Library of Medicines, NIH and European PMC have reported many these derivatives. Some of derivatives have reported to have promising anti-bacterial, cytotoxic, antifungal, anti-inflammatory activities. Recently Ultrasound and Microwave promoted synthesis has shown promising results in synthesis of these derivatives. Many exciting prospects await for its exploitation in this fields.

ISOLASI DAN IDENTIFIKASI SENYAWA ANTIOKSIDAN 2-ETILHEKSIL-4-METOKSISINAMAT DARI EKSTRAK BIJI ALPUKAT (Persea americana Mill.)

<em><span lang="EN-US">Avocado (</span></em><span lang="EN-US">Persea americana</span><em><span lang="EN-US"> Mill.) is a plant widely found in tropical regions such as Indonesia. Currently, people only consume the avocado flesh and dispose of the seed. This study aimed to examine the antioxidant activity, isolate and identify the active antioxidant structure from avocado seed extracts. The trial was conducted from January to June 2021 at the Chemical Laboratory of Natural Substance, Research Center for Biotechnology, LIPI. The avocado fruit used in this research was obtained from Cibitung Central Market, Bekasi. The solvents used in the extraction were n-hexane, ethyl acetate, 96% ethanol, and water with multilevel extraction. Antioxidant activity was tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical method. The structure of the active compound was determined using UV-Vis spectrophotometry, Fourier Transformation Infrared Spectroscopy (FTIR), and GCMS. The 96% ethanol extract had the highest antioxidant activity with EtOH.4.3.1 isolate as the most active antioxidant isolate with IC50 23,07±1,63 μg.ml-1. The identification results of isolate EtOH.4.3.1 of avocado seed extract with UV-Vis spectrophotometry, FTIR, and GCMS indicated 2-Ethylhexyl-4-methoxycinnamate acting as an antioxidant. Further analysis with Nuclear Magnetic Resonance (NMR) spectrometry of protons and carbon is required to determine the number and position of protons and carbon in the chemical structure.</span></em>

NMR-Based Metabolomics Approach to Investigate the Effects of Fruits of Acanthopanax sessiliflorus in a High-Fat Diet Induced Mouse Model

The prevalence of obesity is rapidly increasing and is recognized as a serious health problem. To investigate metabolic changes in an obese model after administration of Acanthopanax sessiliflorus, mice were divided into four groups: normal diet, high-fat diet (HFD), HFD with treatment fenofibrate, and A. sessiliflorus fruit extract. The liver tissue of mice was analyzed using nuclear magnetic resonance (NMR) spectrometry-based metabolomics. In multivariate statistical analyses, the HFD group was discriminated from the normal diet group, and the group fed A. sessiliflorus fruit was discriminated from the HFD group. In biomarker analysis between the HFD group and the group fed A. sessiliflorus fruit, alanine, inosine, formate, pyroglutamate, taurine, and tyrosine, with AUC values of 0.7 or more, were found. The levels of these metabolites were distinguished from the HFD mouse model. Changes in these metabolites were confirmed to act on metabolic pathways related to antioxidant activity.

Chemical Variability of Peel and Leaf Essential Oils in the Citrus Subgenus Papeda (Swingle) and Few Relatives

The Papeda Citrus subgenus includes several species belonging to two genetically distinct groups, containing mostly little-exploited wild forms of citrus. However, little is known about the potentially large and novel aromatic diversity contained in these wild citruses. In this study, we characterized and compared the essential oils obtained from peels and leaves from representatives of both Papeda groups, and three related hybrids. Using a combination of GC, GC-MS, and 13C-NMR spectrometry, we identified a total of 60 compounds in peel oils (PO), and 76 compounds in leaf oils (LO). Limonene was the major component in almost all citrus PO, except for C. micrantha and C. hystrix, where β-pinene dominated (around 35%). LO composition was more variable, with different major compounds among almost all samples, except for two citrus pairs: C. micrantha/C. hystrix and two accessions of C. ichangensis. In hybrid relatives, the profiles were largely consistent with their Citrus/Papeda parental lineage. This high chemical diversity, not only among the sections of the subgenus Papeda, but also between species and even at the intraspecific level, suggests that Papeda may be an important source of aroma diversity for future experimental crosses with field crop species.

Rhizosphere Bacterium Rhodococcus sp. P1Y Metabolizes Abscisic Acid to Form Dehydrovomifoliol

The phytohormone abscisic acid (ABA) plays an important role in plant growth and in response to abiotic stress factors. At the same time, its accumulation in soil can negatively affect seed germination, inhibit root growth and increase plant sensitivity to pathogens. ABA is an inert compound resistant to spontaneous hydrolysis and its biological transformation is scarcely understood. Recently, the strain Rhodococcus sp. P1Y was described as a rhizosphere bacterium assimilating ABA as a sole carbon source in batch culture and affecting ABA concentrations in plant roots. In this work, the intermediate product of ABA decomposition by this bacterium was isolated and purified by preparative HPLC techniques. Proof that this compound belongs to ABA derivatives was carried out by measuring the molar radioactivity of the conversion products of this phytohormone labeled with tritium. The chemical structure of this compound was determined by instrumental techniques including high-resolution mass spectrometry, NMR spectrometry, FTIR and UV spectroscopies. As a result, the metabolite was identified as (4RS)-4-hydroxy-3,5,5-trimethyl-4-[(E)-3-oxobut-1-enyl]cyclohex-2-en-1-one (dehydrovomifoliol). Based on the data obtained, it was concluded that the pathway of bacterial degradation and assimilation of ABA begins with a gradual shortening of the acyl part of the molecule.

Semi-Batch Gasification of Refuse-Derived Fuel (RDF)

Gasification is a promising technology for the conversion of mixed solid waste like refuse-derived fuel (RDF) and municipal solid waste (MSW) into a valuable gas consisting of H2, CO, CH4 and CO2. This work aims to identify the basic challenges of a single-stage batch gasification system related to tar and wax content in the producer gas. RDF was first gasified in a simple semi-batch laboratory-scale gasification reactor. A significant yield of tars and waxes was received in the produced gas. Waxes were analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectrometry. These analyses indicated the presence of polyethylene and polypropylene chains. The maximum content of H2 and CO was measured 500 sec after the start of the process. In a second series of experiments, a secondary catalytic stage with an Ni-doped clay catalyst was installed. In the two-stage catalytic process, no waxes were captured in isopropanol and the total tar content decreased by approximately 90 %. A single one-stage semi-batch gasification system is not suitable for RDF gasification; a large fraction of tar and waxes can be generated which can cause fouling in downstream processes. A secondary catalytic stage can significantly reduce the tar content in gas.

Freitalite, C₁₄H₁₀, a new aromatic hydrocarbon mineral from Freital, Saxony, Germany

The new mineral species freitalite, C14H10, corresponding to the aromatic hydrocarbon anthracene, has been discovered on the mine dump of the Königin Carola shaft (also named Paul Berndt Mine), Freital, near Dresden, Saxony, Germany. The mineral forms thin blades or flakes of irregular shape up to a few millimetres in size and shows an intense violet or whitish-violet to white colour. Freitalite is a product of pyrolysis of coal at low oxygen fugacity and was formed by sublimation from a gas phase. The mineral is associated with sulfur and hoelite. Elemental analysis gave (in wt. %, average of three analyses) C 94.07, H 5.571 and total 99.641. The empirical formula is C14.00H9.88 (calculated for C = 14). The identity with anthracene was confirmed by infrared and Raman spectroscopy, high-performance liquid chromatography, gas chromatography with mass spectrometry, 1H and 13C NMR spectrometry, and X-ray powder diffraction. Freitalite is monoclinic, P21∕a, with lattice parameters a=8.5572(9), b=6.0220(5), c=11.173(1) Å, β=124.174(1)∘ and V=476.34(3) Å3 refined from powder data. The calculated density of 1.242 g cm−3 (for Z=2) is very close to the measured density of 1.240 g cm−3. Freitalite was accepted as a new mineral by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA 2019-116).