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Graphical abstract Highlights • Extracts and compounds from G. asphodeloides proved potent α -glucosidase inhibitors. • 1 showed the strongest α -glucosidase inhibitory effect among the isolated compounds. • 1 was approximately 61 fold more effective than positive control, acarbose. • 2 , 3 and 4 were competitive; 1 and 6 were uncompetitive inhibitors. • Molecular docking studies gave insights into inhibition mechanisms of the compounds. Abstract Some Geranium species have been used to treat diabetes. To evaluate the scientific basis of this ethnopharmacological use, we aimed to isolate potent α -glucosidase inhibitory metabolites of Geranium asphodeloides Burm. through in vitro bioactivity-guided fractionation. All the tested extracts showed high α -glucosidase inhibitory effect compared to acarbose. Among the tested extracts, the ethyl acetate subextract showed the highest activity with an IC 50 value of 0.85 ± 0.01 µM. A hydrolysable tannin, 1,2,4-tri- O -galloyl- β - d -glucopyranose (1), and five flavonoid glycosides, kaempferol-3- O - α -rhamnopyranoside (2), kaempferol-3- O - α -arabinofuranoside (3), quercetin-3- O - β -glucopyranoside (4), quercetin-3- O - α -rhamnopyranoside (5), and quercetin-3- O - α -rhamnofuranoside (6), were isolated from the ethyl acetate subextract. Their structures were identified by 1D- and 2D-NMR experiments. 1 exhibited the highest α-glucosidase inhibitory effect, approximately 61 times more potent than positive control, acarbose, with an IC 50 value of 0.95 ± 0.07 µM. Also, 2 was more potent than acarbose. An enzyme kinetics analysis revealed that compounds 2 , 3 and 4 were competitive, whereas 1 and 6 uncompetitive inhibitors. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolated compounds in the light of the enzyme kinetic studies using various binding sites of the enzyme model. [ABSTRACT FROM AUTHOR]

Abstract: Dihydroxyacetone phosphate (DHAP)‐dependent rhamnulose aldolases display an unprecedented versatility for ketones as electrophile substrates. We selected and characterized a rhamnulose aldolase from Bacteroides thetaiotaomicron (RhuABthet) to provide a proof of concept. DHAP was added as a nucleophile to several α‐hydroxylated ketones used as electrophiles. This aldol addition was stereoselective and produced branched‐chain monosaccharide adducts with a tertiary alcohol moiety. Several aldols were readily obtained in good to excellent yields (from 76 to 95 %). These results contradict the general view that aldehydes are the only electrophile substrates for DHAP‐dependent aldolases and provide a new C−C bond‐forming enzyme for stereoselective synthesis of tertiary alcohols. [ABSTRACT FROM AUTHOR]

In the present study we aimed to identify the α-glucosidase enzyme inhibitory potential of Potentilla inclinata Vill. MeOH and n -BuOH extracts which possessed remarkable α-glucosidase enzyme inhibitory effects with IC 50 values of 1.06 ± 0.02 and 0.93 ± 0.01 μg/ml respectively, compared to that of acarbose (IC 50 31.92 ± 0.17). Thus, BuOH extract was chosen for further phytochemical investigations. A phenolic acid, six flavonol glycosides, and two hydrolysable tannins were isolated from the most active n -BuOH extract of the title plant. Structures of the isolated compounds were elucidated by 1D- and 2D-NMR experiments. All the compounds exhibited remarkable α-glucosidase inhibitory activity compared to the positive control, acarbose. Rutin ( 2 ) showed the highest activity with an IC 50 value of 26.31 ± 0.02 μg/ml. An enzyme kinetics analysis revealed that compounds 5 and 7 were competitive, 4 and 6 noncompetitive, and 3 was uncompetitive inhibitors of α-glucosidase enzyme. Molecular docking studies were performed to get insights into inhibition mechanisms of the isolates considering their inhibition type using various binding sites of the enzyme model we previously reported. [ABSTRACT FROM AUTHOR]

Series of seventeen new multihalogenated 1-hydroxynaphthalene-2-carboxanilides was prepared and characterized. All the compounds were tested for their activity related to the inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 1-Hydroxy-N-phenylnaphthalene-2-carboxamides substituted in the anilide part by 3,5-dichloro-, 4-bromo-3-chloro-, 2,5-dibromo- and 3,4,5-trichloro atoms were the most potent PET inhibitors (IC50 = 5.2, 6.7, 7.6 and 8.0 µM, respectively). The inhibitory activity of these compounds depends on the position and the type of halogen substituents, i.e., on lipophilicity and electronic properties of individual substituents of the anilide part of the molecule. Interactions of the studied compounds with chlorophyll a and aromatic amino acids present in pigment-protein complexes mainly in PS II were documented by fluorescence spectroscopy. The section between P680 and plastoquinone QB in the PET chain occurring on the acceptor side of PS II can be suggested as the site of action of the compounds. The structure-activity relationships are discussed. [ABSTRACT FROM AUTHOR]

The aerial parts of Alchemilla L. species (Rosaceae) are used internally as diuretic, laxative, tonic and externally for wound healing in Turkish folk medicine. Antioxidant effects of the extracts, fractions and isolated compounds from the aerial parts of A. barbatiflora Juz. were investigated with following methods: 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide radical scavenging (SOD), phosphomolibdenum-reducing antioxidant power (PRAP), ferric-reducing antioxidant power (FRAP) assays. In addition, tyrosinase, α-glucosidase and acetylcholinesterase inhibition activities of samples were analyzed. The methanol extract from the aerial parts of plant was consecutively fractionated into four subextracts; n-hexane, chloroform, and remaining water extracts. Further studies were carried out on the most active water subextract and the fractions obtained from water subextract with column chromatography. Phytochemical studies on active fractions of the water subextract led to the isolation of seven metabolites including catechin (1) and a catechin dimer; procyanidin B3 (2), a flavonol glucuronide; quercetin-3-O-β-D-glucuronic acid (miquelianin) (3) with flavonoid glycosides; quercetin-3-O-β-D-galactoside (hyperoside) (4), quercetin-3-O-β-D-arabinoside (guaiaverin) (5), kaempferol-3-O-β-Dxylopyranoside (6) and kaempferol-3-O-(6"-coumaroyl-β-D-glycoside) (tiliroside) (7). Their structures were elucidated by spectral techniques (1D and 2D NMR). The experimental data verified that procyanidin B3 displayed remarkable enzyme inhibitory activity among the whole isolated compounds. [ABSTRACT FROM AUTHOR]

Acid-catalyzed cyclization of spirocyclic 1′-benzyl-2′-(prop-2-en-1-yl)spiro[indole-3,3′-pyrrolidine]-5′-one ( 1 ) was performed. The pentacyclic product of Povarov-like imino-Diels-Alder reaction was isolated in high yield instead of expected tetracyclic aza -Prins intermediate. The unusual exotic alkaloid-type structure of the resulting molecule 2 was unambiguously confirmed by a detailed NMR analysis using a set of 2D NMR spectra including an INADEQUATE experiment. The relative configuration of 2 was predicted from the synthesis mechanism and DFT geometry calculations and independently confirmed using NOESY and residual dipolar coupling (RDC) assisted NMR analysis in stretched crosslinked polystyrene gels. The reversibility of the cycloaddition in aprotic solvents was observed. A new reaction pathway yielding a rare 6-5-5-5 tetracyclic spiroindoline 3 was suggested. The relative configuration within the tetracyclic framework was ultimately proved using Single-crystal X-ray diffraction analysis of compound 4 . [ABSTRACT FROM AUTHOR]

A series of nineteen N-(alkoxyphenyl)-2-hydroxynaphthalene-1-carboxamides and a series of their nineteen positional isomers N-(alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides were prepared and characterized. Primary in vitro screening of all the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, M. kansasii and M. smegmatis. Screening of the cytotoxicity of the compounds was performed using human monocytic leukemia THP-1 cells. Some of the tested compounds showed antimycobacterial activity comparable with or higher than that of rifampicin. For example, 2-hydroxy-N-(4-propoxyphenyl)-naphthalene-1-carboxamide showed the highest activity (MIC = 12 μM) against M. tuberculosis with insignificant cytotoxicity. N-[3-(But-2-yloxy)phenyl]- and N-[4-(but-2-yloxy)phenyl]-2-hydroxy-naphthalene-1-carboxamide demonstrated high activity against all tested mycobacterial strains and insignificant cytotoxicity. N-(Alkoxyphenyl)-1-hydroxynaphthalene-2-carboxamides demonstrated rather high effect against M. smegmatis and M. kansasii and strong antiproliferative effect against the human THP-1 cell line. Lipophilicity was found as the main physicochemical parameter influencing the activity. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay. Structure-activity relationships are discussed. [ABSTRACT FROM AUTHOR]

A new class of superabsorbent hydrogels was synthesized by copolymerization of acrylamide with sodium 4-hydroxy-2-methylenebutanoate (SHMB). SHMB is obtained by saponification of α-methylene-γ-butyrolactone (MBL) which is a renewable monomer from tulips. Radical polymerization of SHMB was studied for the first time. The extent of side products through the ring closure depended on the pH used during the polymerization. Reactivity ratios for copolymerization of SHMB with acrylamide were estimated. Prepared hydrogels with various composition were investigated for their swelling, mechanical and thermal properties, and morphology as well as cytotoxicity. The achieved degree of swelling of the hydrogels was up to 82 000% and significantly exceeds the capacity of classical superabsorbent hydrogels made of acrylamide and salts of acrylic acid. The degree of swelling as well as mechanical and thermal properties of the hydrogels could be tuned by SHMB content. [ABSTRACT FROM AUTHOR]

Composition of humic acids (HA) is a function of plant-derived inputs, degradation processes regulated by microorganisms, organo-mineral interactions and age. Characterization of different origin humic substances is important for evaluation of their contribution to stabile and labile carbon pool in the environment. The relative abundance of chemical components in HA isolated from soils, compost, commercial lignohumates, alginite, acadiane and lignite was studied with aim to quantify content of important biomarkers such as amino acid, lipids and polyphenols. HA were considered as a heterogeneous complex and high concentration of peptides, polyphenols and lipids was determined in acadian-HA to compare with soil-HA. Compost-HA contained much more amino acids to compare with soil-HA samples. Alginite-HA and lignite-HA were similar in biomarkers content to soil-HA. Fourier transform infrared spectroscopy confirmed that chemical composition and functional groups content differs with the origin, humification degree and the age of studied samples. Soil-HA are typically composed of a variety of −OH, COOH−, C–O, C–H2, (aliphatic and aromatic) groups, quinines, lignin fragments, polysaccharide, monosaccharide and proteins fragments, which are linked together by −O−, −NH−, −H=, >C=O, metal ions and –S− groups.13C NMR spectroscopy showed that aromatic carbon content was the highest in lignite-HA and soil-HA. [ABSTRACT FROM AUTHOR]

In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Some of the tested compounds showed the antimycobacterial activity against M. avium subsp. paratuberculosis comparable with or higher than that of rifampicin. 8-Hydroxy- N -[3-(trifluoromethyl)phenyl]- and 8-hydroxy- N -[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide showed MIC = 24 μM against all tested mycobacterial strains. 3-Methoxyphenyl- and 3-methylphenyl derivatives expressed MIC = 27 or 29 μM also against all the tested strains. Their activity against M. avium subsp. paratuberculosis was 4-fold higher than that of rifampicin. 2-Bromophenyl- and 2-(trifluoromethyl)phenyl derivatives had MIC = 23 or 24 μM against M. tuberculosis . A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of cytotoxicity of the compounds was performed using the THP-1 cells, and no significant lethal effect was observed up to tested concentration 30 μM. The structure–activity relationships are discussed. [ABSTRACT FROM AUTHOR]

The aim of study was to search for new biomarkers with a magnetic resonance technique to identify the early stages of dementia, induced by d -galactose, and evaluate Simvastatin therapy. Localized proton magnetic resonance spectroscopy measurements showed a significant decrease in the concentration of N-acetylaspartate + N-acetylaspartylglutamate and myo-inositol in the d -galactose group compared to the control group, and, conversely, an increase of N-acetylaspartate + N-acetylaspartylglutamate in the d -galactose/Simvastatin group. Using a saturation transfer experiment, with phosphorus magnetic resonance spectroscopy, we observed a significant elevation of the forward rate constant of the creatine kinase reaction in the brains of the d -galactose group compared to controls, and subsequently, a significant reduction of this reaction in the d -galactose/Simvastatin group. Spatial learning and memory were evaluated using the modified Morris water maze test. The dynamics of the learning process represented by the learning index revealed a significant reduction in learning in the d -galactose group, but the deficits as a consequence of the d -galactose effects were recovered in the d -galactose/Simvastatin group, in which the learning dynamics resembled those of the control group. By determining the thiobarbituric acid reactive substances and total coenzyme Q 9 in plasma, we have shown that long-term administration of d -galactose created conditions for oxidative stress, and that the administration of Simvastatin decreased oxidative stress in plasma. Volumetry analyses from the hippocampal area show a reduction in the segmented area in the d -galactose group, compared with the control group, and an enlarged area in the hippocampus in the d -galactose/Simvastatin group. [ABSTRACT FROM AUTHOR]

In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Derivatives substituted by trifluoromethyl, bromo, methyl and methoxy moieties in C′ (3) and C′ (4) positions of the anilide ring showed 2-fold higher activity against M. tuberculosis than isoniazid and 4.5-fold higher activity against M. avium subsp. paratuberculosis than rifampicin. 6-Hydroxy- N -(2-methylphenyl)naphthalene-2-carboxamide had MIC = 29 μM against M. avium complex. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using the THP-1 cells, and no significant lethal effect was observed. The structure–activity relationships are discussed. [ABSTRACT FROM AUTHOR]

Two new palladium complexes with (1E,6E)-1,7-bis(3,4-diethoxyphenyl)-1,6-heptadiene-3,5-dione, 1 and 2, have been synthesized and structurally characterized. Complex 1 has the molecular structure confirmed by X-ray diffraction measurements. Both complexes display a significant antiproliferative activity against human colorectal cancer cells by inducing early and late apoptotic processes in those cells. [ABSTRACT FROM AUTHOR]

This study presents the comparison of conformational behaviour of two similar push–pull ethylenes in which the possibility to form an intramolecular hydrogen bond exists. The IR, Raman and NMR spectroscopic studies as well as ab initio MP2 and DFT B3LYP theoretical calculations using 6-31G** basis set confirmed that the presence of intramolecular hydrogen bond has an important influence on conformational behaviour of such type compounds. 3-methylamino-2-acetyl propenenitrile (MAAPN) H3C—NH—CH=C(CN)(COCH3) was prepared as pure Z-isomer with intramolecular hydrogen bond while 3-methylamino-2-methylsulfonyl propenenitrile (MASPN) H3C—NH—CH=C(CN)(SO2CH3) as pure E-isomer. MAAPN in polar solutions partially underlies to the isomerization. Such process has not been observed for MASPN which exists in solution in two conformers with the anti and syn orientation of the methylamino group towards the C=C double bond, anti conformer being about 2.0±0.4kJmol−1 more stable. The vibrational spectra of studied molecules were assigned on the base of normal coordinate calculations and potential energy distribution (PED). The use of different polarizable continuum models (IPCM, PCM) included in SCRF theory leads to controversial results in ground-state energy calculations in solutions of various polarity. [Copyright &y& Elsevier]

Abstract: The neuropathological and clinical symptoms of Huntington''s disease (HD) can be simulated in animal model with systemic administration of 3-nitropropionic acid (3-NP). Energy defects in HD could be ameliorated by administration of coenzyme Q10 (CoQ10), creatine, or nicotinamid. We studied the activity of creatine kinase (CK) and the function of mitochondrial respiratory chain in the brain of aged rats administered with 3-NP with and without previous application of antioxidants CoQ10 +vitamin E. We used dynamic and steady-state methods of in vivo phosphorus magnetic resonance spectroscopy (31P MRS) for determination of the pseudo-first order rate constant (k for) of the forward CK reaction, the phosphocreatine (PCr) to adenosinetriphosphate (ATP) ratio, intracellular pHi and Mgi 2+ content in the brain. The respiratory chain function of isolated mitochondria was assessed polarographically; the concentration of CoQ10 and α-tocopherol by HPLC. We found significant elevation of k for in brains of 3-NP rats, reflecting increased rate of CK reaction in cytosol. The function of respiratory chain in the presence of succinate was severely diminished. The activity of cytochromeoxidase and mitochondrial concentration of CoQ10 was unaltered; tissue content of CoQ10 was decreased in 3-NP rats. Antioxidants CoQ10 +vitamin E prevented increase of k for and the decrease of CoQ10 content in brain tissue, but were ineffective to prevent the decline of respiratory chain function. We suppose that increased activity of CK system could be compensatory to decreased mitochondrial ATP production, and CoQ10 +vitamin E could prevent the increase of k for after 3-NP treatment likely by activity of CoQ10 outside the mitochondria. Results of our experiments contributed to elucidation of mechanism of beneficial effect of CoQ10 administration in HD and showed that the rate constant of CK is a sensitive indicator of brain energy disorder reflecting therapeutic effect of drugs that could be used as a new in vivo biomarker of neurodegenerative diseases. [Copyright &y& Elsevier]

Twenty four crossbred (Large White, White Meaty, Pietrain, Hampshire) pigs were tested by DNA probe for a mutation on the ryanodine receptor RYR1 (malignant hyperthermia-MH). An equal number of pigs heterozygote (monomutant-MON) and normal on MH (nonmutant-NON) were used in the experiment. The pigs were fed finisher feed (control group) or finisher feed supplemented with magnesium (3.6 g MgO per pig per day; MgO group) for 5 days prior to slaughter. Pigs fed the diet supplemented with MgO had higher plasma Mg concentrations. Phosphorus nuclear magnetic resonance (31P NMR) measurements on postmortem (15 min) muscle samples (longissimus muscle) showed the highest phosphocreatine levels in normal pigs fed MgO (P<0.05). The MgO supplementation caused increased Ca2+ uptake and Ca2+ ATPase activity only in normal (NON) pigs. ATPase activity was lowest (P<0.05) in heterozygote control pigs. Pigs fed MgO supplemented diet had higher pH (45 min postmortem). A significant lower pH (P<0.05) was obtained in heterozygous (MON) control pigs. Also pigs fed with MgO had lower percentage of drip losses and significant differences (P<0.05) were obtained between heterozygous (MON) pigs. The results indicate that dietary MgO supplementation can improve parameters of muscle energetic metabolism, Ca2+ uptake and meat quality (pH, drip loss). [Copyright &y& Elsevier]

Phosphorus nuclear magnetic resonance (31P NMR) measurements were made to determine muscle energetic metabolism on muscle biopsy samples of heterozygote malignant hyperthermia (Nn) and normal (NN) pigs DNA tested on occurrence of mutation in RYR 1 gene. Biopsy samples (approx. 1 g) were obtained by spring-loaded biopsy instrument (Biotech, Slovakia) from Longissimus dorsi (LD) muscle at 80 kg live weight. The spectra were recorded at 121 MHz on a VXR 300 (Varian) spectrometer in 10 mm diameter tube (maintained at 39 °C) for 50 min. pH of bioptates after NMR measurements were also measured at 60 min. The changes in inorganic phosphate (Pi), phosophocreatine (PCr) and adenosine triphosphate (ATP) were faster in heterozygote malignant hyperthermia (MH; 29 crossbred White Meaty×Pietrain) than in normal (13 Duroc, Yorkshire and White Meaty). The values of PCr at 20 min and pH at 60 min after taking biopsy allowed discrimination between NN and Nn pigs and significant (P<0.05) differences were also found between two subgroups in heterozygote MH pigs with different rate of post mortem muscle metabolism. The values of PCr and pH as measured at definite time on the biopsies, were significantly (P<0.05) correlated with the rate of post mortem metabolism (pH) and with meat quality traits (r approx. 0.4–0.6). The 31P NMR measurements pointed to impaired muscle energetic metabolism connected with the occurrence of mutation on the RYR 1 gene in heterozygote MH pigs. [Copyright &y& Elsevier]

Presents a study which investigates the carbon metabolism of three strains of Fibrobacter succinogenes and one strain of Fibrobacter intestinalis. What is fibrobacter succinogenes; Materials and methods used in study; Results of study.

• A facile synthesis of novel tetrahydrofurfuryl hemiacetals is described for the first time. • Over Pd/CaCO 3 catalyst high yields of tetrahydrofurfuryl hemiacetals are achieved. • Basic sites on a catalyst support enhance the rate of furfuryl hemiacetal formation. • Novel tetrahydrofurfuryl hemiacetals are fully characterized. • The mechanism of reductive acetalization leading to hemiacetals is proposed. An entirely new and highly selective method for preparation of novel tetrahydrofurfuryl hemiacetals is described. The process is based on the catalytic hydrogenation of furfural in an alcohol under mild reaction conditions and at very short reaction times. As a highly active and selective catalyst palladium supported on calcium carbonate is used. Basic sites of the catalyst support enhance the formation of furfuryl hemiacetal as the intermediate which is instantaneously hydrogenated into stable tetrahydrofurfuryl hemiacetal. About 85–90 % yields of tetrahydrofurfuryl hemialkylacetals can be achieved within 20 min by reaction of furfural in alcoholic solutions at 60 °C and 0.3 MPa of hydrogen. The mechanism of reductive acetalization of furfural into tetrahydrofurfuryl hemialkylacetals is proposed. [ABSTRACT FROM AUTHOR]