Effect of dietary conjugated linoleic acid isomers on water and glycerol permeability of kidney membranes

Conjugated linoleic acid (CLA) refers to a group of positional and geometrical isomers of linoleic acid in which the double bonds are conjugated. Dietary CLA has been associated with various health benefits although details of its molecular mode of action remain elusive. The effect of CLA supplemented to palm oil-based diets in Wistar rats, as a mixture of both or isolated c9,t11 and t10,c12 isomers, was examined on water and glycerol membrane permeability of kidney proximal tubule. Although water permeability was unaltered, an increase in glycerol permeability was obtained for the group supplemented with CLA mixture, even though the activation energy for glycerol permeation remained high. This effect was correlated with an increased CLA isomeric membrane incorporation for the same dietary group. These results suggest that diet supplementation with CLA mixture, in contrast to its individual isomers, may enhance membrane fluidity subsequently raising kidney glycerol reabsorption.     

Novel androgen receptor full antagonists: Design,synthesis, and a docking study of glycerol and aminoglycerol derivatives that contain p-carborane cages

Based on the co-crystal structure of bicalutamide with a T877A-mutated androgen receptor (AR), glycerol and aminoglycerol derivatives were designed and synthesized as a novel type of carborane-containing AR modulators. The (R)-isomer of 6c, whose chirality is derived from the glycerol group, showed 20 times more potent cell inhibitory activity against LNCaP cell lines expressing T877A-mutated AR than the corresponding (S)-isomer. Docking studies of both isomers with AR suggested that (R)-6c is in closer spatial proximity to helix-12 of the AR than (S)-6c, which is the most important common motif in the secondary structure of AR for the expression of antagonistic activity.     

Variation von Glycerin,Sorbit und anderen Metabolitgehalten infolge von Temperaturstress bei Larven von Callitroga macellaria

Sorbitol, sorbitol phosphate, glycerol, α-glycerol phosphate, lactic and pyruvic acid were determined after storing of non-feeding Callitroga larvae hot or cold. Compared with controls, the high levels of pyruvic acid and lactic acid indicate the increase of anaerobic metabolism by temperature stress. At the same time glycerol increased about threefold, sorbitol increased about seventeenfold after heating and about thirty-fourfold after cooling. The level of glycerol phosphate is lowered after heating and after cooling. Sorbitol phosphate shows after heating a trend to decrease. Heat causes a great standard error.Based on this and other facts it is supposed that different kinds of stress result in a lack of metabolic energy. Thus the pathway of glucose phosphate to direct oxidation and formation of triose phosphate by the pentose phosphate cycle is energetically favoured because the phosphorylation of hexose phosphate to hexose diphosphate is avoided. Triose phosphate can enter the glycolytic pathway. The reduced coenzyme nicotinamide adenine dinucleotide phosphate (NADPH) is generated by the formation of polyols (or polyolphosphates).     

Enzymatic synthesis of 1,3-dihydroxyphenylacetoyl-sn-glycerol: Optimization by response surface methodology and evaluation of its antioxidant and antibacterial activities

In this study, the enzymatic synthesis of phenylacetoyl glycerol ester was carried out as a response to the increasing consumer demand for natural compounds. 1,3-dihydroxyphenylacetoyl-sn-Glycerol (1,3-di-HPA-Gly), labeled as “natural” compound with interesting biological properties, has been successfully synthesized for the first time in good yield by a direct esterification of glycerol (Gly) with p-hydroxyphenylacetic acid (p-HPA) using immobilized Candida antarctica lipase as a biocatalyst. Spectroscopic analyses of purified esters showed that the glycerol was mono- or di-esterified on the primary hydroxyl group. These compounds were evaluated for their antioxidant activity using two different tests. The glycerol di-esters (1,3-di-HPA-Gly) showed a higher antiradical capacity than that of the butyl hydroxytoluene. Furthermore, compared to the p-HPA, synthesized ester (1,3-di-HPA-Gly) exhibited the most antibacterial effect mainly against Gram + bacteria. Among synthesized esters the 1,3-di-HPA-Gly was most effective as antioxidant and antibacterial compound. These findings could be the basis for a further exploitation of the new compound, 1,3-di-HPA-Gly, as antioxidant and antibacterial active ingredient in the cosmetic and pharmaceutical fields.     

Stereochemistry of octopine and of its isomers and their enzymatic properties

The four isomers of octopine were prepared from pyruvic acid and l- or d-arginine and from α-keto δ-guanidinovaleric acid and l- or d-alanine by reduction with sodium cyanoborohydride. The absolute configuration of d-octopine, the natural occurring isomer being S(l) at the arginine center, and R(d) at the alanine center, was confirmed enzymatically. d-Octopine is the only isomer oxidized by NAD⁺ in the presence of octopine dehydrogenase from Pecten maximus L. The isomer with configuration S(l) at the alanine center is found to be a competitive inhibitor. Isomers with R(d) configuration at the arginine center show no detectable effect on the enzymatic reaction.     

Analysis of some partly and fully esterified oligogalactopyranuronic acids by p.m.r. spectrometry at 220 MHz

The p.m.r. spectra of mono-, di-, tri-, tetra-, and penta-galactopyranuronic acids (1–5), the corresponding fully esterified methyl esters (6–10), the partly esterified di- (11) and tri-galactopyranuronic acids (12, 13), and the unsaturated di-, tri-, and tetra-galactopyranuronic acids (14–16) were measured on solutions in D₂O at 220 MHz at a pH of 1 and 6. Observation of doublets (J 4 Hz) in the range δ 4.90–5.05 p.p.m. indicates the site of esterification in the non-reducing or reducing sugar residue. Esterification of the sugar residue at the non-reducing end can be deduced from both the presence of a methyl resonance peak at δ 3.80 and the indifference of the signal at δ 4.35 (H-4) to the change in pH. The δ values and coupling constants confirm that all the d-galacturonic acid residues have the CI conformation and are α-(1→4)-linked. In the unsaturated oligogalactopyranuronic acids, the double bond is located between C-4 and C-5 of the sugar unit at the non-reducing end. The 4-deoxyhex-4-enopyranosyluronic acid residue occurs in the ²H₁(d) conformation. Compound 11 was identified as O-(α-d-galactopyranosyluronic acid)-(1→4)-(methyl α,β-d-galactopyranuronate). Compounds 12 and 13 each consisted of a mixture of the three possible isomers; preference for the site of esterification decreases in the order reducing sugar unit, non-reducing sugar unit, sugar unit at the non-reducing end.     

Nuclear magnetic resonance studies on pyridine dinucleotides. Carbon-13 assignments and structure determination of NADHX and the primary acid product of NADH.

The ¹³C spectra of β-NADH, NADHX, and the primary acid product of NADH were obtained and assigned. The conversion of the NADHX isomers to the two isomers of NADH acid product is demonstrated through the use of ¹³C-enriched compounds. The structure of NADHX is assigned as β-6-hydroxy-1,4,5,6-tetrahydronicotinamide adenine dinucleotide and the structures of the primary acid products of NADH are assigned as α-O^2′-6B-cyclotetrahydronicotinamide adenine dinucleotide and α-O^2′-6A-cyclotetrahydronicotinamide adenine dinucleotide.The structures of NADHX and the major isomer of the primary acid product, derived from studies of model compounds, are consistent with those proposed by Oppenheimer and Kaplan [Biochemistry (1974) 13, 4675, 4685]. However, the spectra of ¹³C-enriched primary acid product also demonstrated the existence of the A isomer which was not observed in the latter ¹H study. The A and B isomers were found to exist in the same ratio even when the primary acid product was formed directly from NADHX. This observation is discussed in terms of the previously proposed mechanism for the acid decomposition of NADH.     

Parallel RNA-strand recognition by 2′-amino-β-l-LNA

A short synthetic route to the first β-l-ribo configured locked nucleic acid (LNA), that is, 2′-amino-β-l-LNA thymine phosphoramidite 6, has been developed from bicyclic nucleoside 1. Incorporation of 2′-amino-β-l-LNA thymine monomers into α-DNA strands results in probes forming stable duplexes with complementary RNA in parallel orientation.     

The influence of monoterpenoids and phenol derivatives on Drosophila melanogaster viability

The present study investigated the effect of mono/bicyclic terpenoids and phenol derivatives on the viability of Drosophila melanogaster and their influence on the multiplication of the nuclear genome. The fertility and viability of fruit flies were assessed after oral administration and inhalation exposure of compounds 1–5: guaiacol, eugenol, borneol, menthol and carvacrol. The influence of terpenoids and phenols on the degree of chromosomes polyteny in salivary gland cells of D. melanogaster larvae was determined. Among all tested compounds, carvacrol demonstrated the most significant impact on fecundity and insect survival when inhaled or adding to the culture medium. Oral administration of carvacrol had an impact on giant chromosomes increasing their average level of chromosome polyteny degree while eugenol adding to culture medium had the opposite effect. The possible mechanism of terpenoids and phenols action is discussed.     

Synthesis and biological activity of (24E)- and (24Z)-26-hydroxydesmosterol

Using 3β-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol synthesis is high. Unlike desmosterol (1), neither of these isomers is a ligand to the liver x receptors and thus represents a novel biological deactivation mechanism avoiding cholesterol synthesis.     

Conformational studies on l-amino-l-deoxypentitols

The conformations of the four 1-amino-1-deoxy-D-pentitols and their hydrochlorides in deuterium oxide solution have been analyzed by 250-MHz, ¹H-n.m.r. spectroscopy. The data indicate that the D-arabino (2) and D-lyxo (3) isomers adopt extended, planar, zigzag conformations, whereas the D-xylo (4) and D-ribo (1) isomers have the carbon chain in a nonplanar, “sickle” arrangement. The conformational assignments parallel closely those previously advanced for various related series of acetylated derivatives in organic solvents, and for nonacetylated analogs in solution and in the crystalline state. The spectral changes that take place in solution upon converting the amines 1–4 into their amine-salt forms are discussed, and the conformational data are considered in relation to the reactivity of 1–4 on deamination with nitrous acid and with respect to related reactions leading to ring closure under kinetic conditions.     

Automated determination of monosaccharides using p-hydroxybenzoic acid hydrazide.

An automated procedure has been described based on the manual method of Hagen and Hagen [(1962) Canad. J. Biochem.40, 1129] which will rapidly and reproducibly measure glycerol concentrations. The method was developed primarily for the determination of glycerol in adipose tissue and various incubation media. The glycerol in solution is estimated by its partial conversion to dihydroxyacetone by glycerol dehydrogenase from Aerobacter aerogenes. The range of glycerol concentrations able to be measured is more extensive than with other automated methods.     

Scaffold-switching: An exploration of 5,6-fused bicyclic heteroaromatics systems to afford antituberculosis activity akin to the imidazo[1,2-a]pyridine-3-carboxylates

A set of 5,6-fused bicyclic heteroaromatic scaffolds were investigated for their in vitro anti-tubercular activity versus replicating and non-replicating strains of Mycobacterium tuberculosis (Mtb) in an attempt to find an alternative scaffold to the imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidines that were previously shown to have potent activity against replicating and drug resistant Mtb. The five new bicyclic heteroaromatic scaffolds explored in this study include a 2,6-dimethylimidazo[1,2-b]pyridazine-3-carboxamide (7), a 2,6-dimethyl-1H-indole-3-carboxamide (8), a 6-methyl-1H-indazole-3-carboxamide (9), a 7-methyl-[1,2,4]triazolo[4,3-a]pyridine-3-carboxamide (10), and a 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carboxamide (11). Additionally, imidazo[1,2-a]pyridines isomers (2 and 12) and a homologous imidazo[1,2-a]pyrimidine isomer (6) were prepared and compared. Compounds 2 and 6 were found to be the most potent against H₃₇Rv Mtb (MIC’s of 0.1 μM and 1.3 μM) and were inactive (MIC >128 μM) against Staphylococcus aureus, Escherichia coli and Candida albicans. Against other non-tubercular mycobacteria strains, compounds 2 and 6 had activity against Mycobacterium avium (16 and 122 μM, respectively), Mycobacterium kansasii (4 and 19 μM, respectively), Mycobacterium bovis BCG (1 and 8 μM, respectively) while all the other scaffolds were inactive (>128 μM).     

Glycerols and fatty acids isolated from Micractinium sp. KSF0031

From the collected extract from King Sejong Antarctic Station, strain Micractinium sp. KSF0031, led to the isolation of one new monoacyldigalactosyl glycerol (1) and seven known compounds (2–8). Their chemical structures were established using extensive spectroscopic techniques, including 1D, 2D-NMR, and MS, and compared with the published data. To the best of our knowledge, this is the first report to investigate the secondary metabolites from genus Micractinium. The monoacyldigalactosyl glycerol in Micractinium could serve as its chemotaxonomic markers.     

New C9-polyacetylenes from the essential oil of the highly endangered species Baccharis palustris Heering (Asteraceae)

The essential oil composition of the aerial parts from Baccharis palustris Heering (Asteraceae), a highly endangered species, was analyzed by GC/qMS, GC/HRMS-TOF, FT-IR, UV–vis and NMR spectroscopy using 1D and 2D techniques. To our knowledge, this is the first report on the essential oil composition of B. palustris, as well as the first phytochemical study on this plant species. The volatile extracts were obtained from different phenologicals stages of plant, at flowering stage (FS) and vegetative stage (VS), where 51 components were identified accounting for 96.3 % and 99.0 % of the oil, respectively. The oil was rich in polyacetylene compounds (> 75 %), being the main components identified the new natural C₉-polyacetylenes 1-nonene-3,5-diyne (1, here named as baccharisdiyne) (52.7–65.0 %), 1,7(Z)-nonadiene-3,5-diyne [2, 7(Z)-dehydro-baccharisdiyne] (14.4–17.8 %), and 1,7(E)-nonadiene-3,5-diyne [3, 7(E)-dehydro-baccharisdiyne] (1.5–2.4 %). In addition, the known polyacetylenic compounds (Z)-lachnophyllum acid methyl ester (4) (4.3–5.3 %) and (E)-lachnophyllum acid methyl ester (5) (0.2 %) were also identified. Moreover, GC/qMS analysis allowed the identification of other 46 components in the essential oil samples, mainly mono- and sesquiterpenoids. In B. palustris, C₉-polyacetylenes probably derive biogenetically from a C₁₀ precursor: baccharisdiyne (1) would be derived from either or both lachnophyllum methyl ester geometric isomers (4 or 5), by enzymatic hydrolysis followed by decarboxylation. Dehydro-baccharisdiynes (2 and 3) could be produced by a similar pathway starting from the corresponding matricaria acid methyl ester isomers, one of which was tentatively identified at trace-level in B. palustris essential oil.     

Structure–activity relationship of antiparasitic and cytotoxic indoloquinoline alkaloids,and their tricyclic and bicyclic analogues

Based on the indoloquinoline alkaloids cryptolepine (1), neocryptolepine (2), isocryptolepine (3) and isoneocryptolepine (4), used as lead compounds for new antimalarial agents, a series of tricyclic and bicyclic analogues, including carbolines, azaindoles, pyrroloquinolines and pyrroloisoquinolines was synthesized and biologically evaluated. None of the bicyclic compounds was significantly active against the chloroquine-resistant strain Plasmodium falciparum K1, in contrast to the tricyclic derivatives. The tricyclic compound 2-methyl-2H-pyrido[3,4-b]indole (9), or 2-methyl-β-carboline, showed the best in vitro activity, with an IC₅₀ value of 0.45 μM against P. falciparum K1, without apparent cytotoxicity against L6 cells (SI > 1000). However, this compound was not active in the Plasmodium berghei mouse model. Structure–activity relationships are discussed and compared with related naturally occurring compounds.     

An unusual caffeic acid derived bicyclic [2.2.2] octane lignan and other constituents from Cordia rufescens

This work reports isolation of an unusual lignan with a bicyclic [2.2.2] octene skeleton, named rufescenolide (1), from stems of Cordia rufescens, along with β-sitosterol, stigmasterol, syringaldehyde, 3-β-O-d-glucopyranosyl-sitosterol, methyl caffeate, 4-methoxy-protocatechuic acid and methyl rosmarinate. Structural characterizations employed IR spectroscopic, ESIHRMS and mono and dimensional NMR spectroscopy.     

Vernoguinamide: A new ceramide and other compounds from the root of Vernonia guineensis Benth. and their chemophenetic significance

The chemical investigation of the roots of Vernonia guineensis Benth. (Asteraceae) resulted in the isolation of a new ceramide, named vernoguinamide (1), together with fifteen known compounds, including three anthraquinones, physion (2), erythroglaucin (3) and emodin (4), three triterpenoids, hop-17(21)-en-3β-yl acetate (5), lupeol (6) and betulinic acid (7), six steroids, vernoguinoside A (8), vernoguinoside (9), β-sitosterol 3-O-β-D-glucoside (10), stigmasterol 3-O-β-D-glucoside (11), stigmasterol (12) and β-sitosterol (13) and three fatty acid derivatives, tetracosanoic acid (14), tricosanic acid (15) and arachidic acid glycerol ester (16). The structure of the new compound as well as those of the known compounds were established by spectrometric analysis including HRESI-MS, 1D and 2D-NMR and by comparison with the previously reported data. Among these compounds, the anthraquinones 2–4 and the triterpene 5 were isolated for the first time from Vernonia genus and compounds 6, 7 and 14–16 were extracted for the first time from the species. The isolated compounds were tested for their antibacterial activity and 3, 8 and 9 were the most active compounds against the tested bacteria. Furthermore, the chemophenetic relationships of the isolated compounds and their significance were also discussed.     

Growth-Related Substituent Changes in Exopolysaccharides of Fast-Growing Rhizobia

Pyruvic acid and O-acetyl groups are the major noncarbohydrate substituents in exopolysaccharides (EPS) produced by fast-growing species of Rhizobium. EPS substituent variations were observed among strains of the same species. The amounts of these substituents also varied with culture age; pyruvic acid increased in the EPS of all four species, whereas O-acetyl increased in Rhizobium trifolii and R. leguminosarum EPS, decreased in R. meliloti EPS, and remained constant in R. phaseoli EPS. The use of glycerol as a substrate for R. meliloti significantly increased EPS yields, whereas mannitol increased those of the other three Rhizobium species.