Malyngic acid,a new fatty acid from Lyngbya majuscula

Malyngic acid, a major fatty acid in several varieties of the marine blue-green alga Lyngbya majuscula, has been determined to be 9(S),12(R),13(S)-trihydroxyoctadeca-10(E),15(Z)-dienoic acid from chemical and spectral data and by its conversion to 9(S),12(R),13(S)-trihydroxystearic acid and degradation to 2-deoxy-D-ribitol.     

In vitro metabolism of a new cardioprotective agent, KR-32570, in human liver microsomes

KR-32570 (5-(2-methoxy-5-chlorophenyl)furan-2-ylcarbonyl)guanidine) is a new reversible Na+/H+ exchanger inhibitor for preventing ischemia-reperfusion injury. This study was performed to identify the metabolic pathway of KR-32570 in human liver microsomes. Human liver microsomal incubation of KR-32570 in the presence of NADPH and UDPGA resulted in the formation of six metabolites, M1-M6. M1 was identified as O-desmethyl-KR-32570, on the basis of liquid chromatography/tandem mass spectrometric (LC/MS/MS) analysis with the synthesized authentic standard. M2 and M3 were suggested to be hydroxy-KR-32570 and hydroxy-O-desmethyl-KR-32570, respectively. M1, M2, and M3 were further metabolized to their glucuronide conjugates, M4, M5, and M6, respectively. In addition, the specific P450 isoforms responsible for KR-32570 oxidation to two major metabolites, O-desmethyl-KR-32570 and hydroxy-KR-32570, were identified using a combination of correlation analysis, chemical inhibition in human liver microsomes and metabolism by expressed recombinant P450 isoforms. The inhibitory potency of KR-32570 on clinically major P450s was investigated in human liver microsomes. The results show that CYP3A4 contributes to the oxidation of KR-32570 to hydroxy-KR-32570, and CYP1A2 play the predominant role in O-demethylation of KR-32570. KR-32570 was found to inhibit moderately the metabolism of CYP2C8 substrates.     

6-Gingesulfonic acid, a new anti-ulcer principle, and gingerglycolipids A, B, and C, three new monoacyldigalactosylglycerols, from zingiberis rhizoma originating in Taiwan.

By monitoring the effects on HCl/ethanol-induced gastric lesions in rats, a new antiulcer principle named 6-gingesulfonic acid was isolated from Zingiberis Rhizoma, the dried rhizome of Zingiber officinale Roscoe (cultivated and processed in Taiwan) together with three new monoacyldigalactosylglycerols named gingerglycolipids A, B and C. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence. 6-Gingesulfonic acid showed more potent anti-ulcer activity than 6-gingerol and 6-shogaol.     

Tagetnoic acid,a new lipoxygenase inhibitor peroxy fatty acid from Tagetes minuta growing in Saudi Arabia

Abstract

A new peroxy fatty acid, tagetnoic acid (5) [4-((3S,6S)-6-((3E,8E)-octadeca-3,8-dien-1-yl)-3,6-dihydro-1,2-dioxin-3-yl)butanoic acid] and four known metabolites: ecliptal (5-formyl-α-terthiophene) (1), 5-(4-hydroxybut-1-ynyl)-2,2′-bithiophene (2), 22,23-dihydrospinasterone (3), and stigmasterol (4) were separated from the n-hexane fraction of the aerial parts of Tagetes minuta L. (Asteraceae). Their chemical structures were verified using IR, UV, 2D and 1D NMR, and HRMS. Compounds 3–5 displayed potent lipoxygenase inhibitory potential with IC₅₀s 2.26, 1.83, and 1.17?μM, respectively compared to indomethacin (IC₅₀ 0.89?μM). Moreover, molecular docking study revealed that the potent activity of 5 is due to H-bonding and hydrophobic interaction. The results of this study suggested that Tagetes minuta dietary consumption would be useful for the individuals at risk of acute and chronic inflammatory disorders.     

Release characteristics of a free polyunsaturated fatty acid from an oily lymphographic agent

The release profiles of a free polyunsaturated fatty acid, alpha-linolenic acid, from solutions in an oily lymphographic agent Lipiodol-Ultra-Fluid (Lipiodol), to rabbit and human plasma, phosphate buffer solution (PBS), and PBS containing bovine serum albumin (BSA) were examined in vitro. The times required for 50% release of alpha-linolenic acid from Lipiodol were about 1 and 1.5 h in the rabbit and human plasma, respectively. Although only a slight amount of alpha-linolenic acid was released from Lipiodol to PBS after 24 h incubation at 37 degrees C, release was markedly enhanced by the addition of BSA to PBS. The amount of alpha-linolenic acid released from Lipiodol into PBS containing 5% BSA increased as the alpha-linolenic acid content in Lipiodol was increased. In all experiments, the release had stopped before all alpha-linolenic acid had been released. The prolongation of alpha-linolenic acid release from Lipiodol is considered a requisite for a selective anticancer effect of Lipiodol containing a free fatty acid on liver cancer.     

Identification of glycerophospholipid fatty acid remodeling by using mass spectrometry imaging in bisphenol S induced mouse liver

Exposure to BPS induced glycerophospholipid fatty acid remodeling, which might be useful in toxicity evaluation for bisphenols-induced hepatic diseases.     

High-performance liquid chromatographic determination of fatty acid binding proteins in rat liver with fluorescence detection.

A highly sensitive, simple and reproducible method for the quantitative determination of fatty acid binding protein in rat liver by post-column high-performance liquid chromatography with fluorescence detection is presented. Fatty acid binding protein in rat liver cytosols is separated by gel-permeation column chromatography, which is followed by fluorescence detection. The detection makes use of the fluorescence enhancement observed when a fluorescent fatty acid probe, dansylundecanoic acid, binds to fatty acid binding protein. The method is rapid, simple to perform and highly sensitive. The method was applied to the determination of fatty acid binding protein in liver from control and hypolipidaemic drug treated rats.     

Effect of essential fatty acid deficiency on activity of liver plasma membrane enzymes in the rat.

Liver plasma membranes (LPM) were isolated from rats fed an essential fatty acid-supplemented diet (+EFA) or from rats fed an essential fatty acid-deficient diet (-EFA). The proportions of linoleate and arachidonate in membrane total fatty acids in the -EFA preparations were one-half or less than the values for the +EFA preparations. Basal, F-, or glucagon-stimulated adenylate cyclase activities were significantly lower in EFA-deficient livers than in nondeficient ones. Addition of GTP significantly enhanced glucagon-stimulated adrenylate cyclase in both groups, but extent of stimulation above basal was greater in EFA-deficient livers. Portal vein injection of glucagon in vivo resulted in significantly higher cAMP formation in +EFA livers than in -EFA livers. When glucagon was used in vitro at 1-1,000 nM, stimulation of adenylate cyclase remained lower in EFA-deficient membranes, but extent of stimulation above basal activity was larger in -EFA membranes than in +EFA. Total Na+, K+ (Mg2+)-ATPase from EFA-depleted LPM exhibited significantly higher values of apparent Km and Vmax-5'-Nucleotidase activity, in contrast, was considerably decreased in EFA-deficient rats. These findings show that, in animals, changes in unsaturated fatty acid composition can affect the properties of membrane-bound enzymes. These alterations could be due to changes in membrane physical properties and/or prostaglandin formation.     

Grape extracts suppress the formation of preneoplastic foci and activity of fatty acid synthase in rat liver

This study was conducted to examine the effects of dietary grape extracts on preneoplastic foci formation in rat hepatocarcinogenesis, and related hepatic enzymes. Male Sprague-Dawley rats were fed basal diet or grape diet containing 15% concentrated grape extracts (68 bricks). The grape diet groups were divided into whole-period grape diet group (DEN-GW; grape diet group fed throughout experimental period) and postinitiation grape diet group (DEN-GP; grape diet group fed from post initiation stage) according to the starting time point of the grape diet. Hepatocarcinogenesis was induced by diethylnitrosamine (DEN; 200 mg/kg bw) and 2/3 partial hepatectomy (DEN-B; DEN-treated basal diet group, DEN-GW, and DEN-GP groups), while the control group treated with saline and sham operation (Control group). The formation of placental glutathione (GSH) S-transferase positive (GST-P+) foci in DEN-GW group was moderately but significantly suppressed, however, not in DEN- GP group. Thiobarbituric acid reactive substances content of DEN-GW group was significantly lower than that of DEN-B group. The activity of fatty acid synthase (FAS) in the grape diet groups was decreased about 1/2 of the DEN-B group. The content of GSH and GSH peroxidase activity were increased by carcinogen treatment, but not modulated by grape diet. The activities of GSH S-transferase, p-nitrophenol hydroxylase, and catalase were not affected by diet or treatment. Conclusively, the grape diet-induced reduction of FAS activity that was expressed highly in neoplastic tissues, might be one of the contributing mechanisms of hepatic cancer prevention.     

Calix[4]arene-cholic acid conjugates: a new class of efficient synthetic ionophores

The synthesis of a new class of amphiphilic calix[4]arene-based ionophores, relying on direct reductive amination as a key step, and the evaluation of their H+ and Na+ transporting properties is described.     

Thermal stability and structure of a new co-crystal of theophylline formed with phthalic acid

A new co-crystal of theophylline and phthalic acid with 1:1 molar ratio has been prepared. It crystallises in the monoclinic crystal system, space group P2₁/c, a=11.5258(9), b=10.1405(6), c=13.9066(12) Å, β=106.827(4)°. The structure of the co-crystal has been revealed by single crystal X-ray diffraction. An infinite helical polymeric chain is formed by intermolecular hydrogen bonds of the two neutral constituents. The hydroxyl group and carbonyl oxygen atom in one of the carboxyl groups of phthalic acid form hydrogen bonds to O6 and to N(7)H atoms of theophylline, respectively, while the other carboxyl OH group of phthalic acid is in hydrogen bond to N9 atom of theophylline by very strong intermolecular interactions proven by 1883 cm^?1 centred peak in FTIR spectrum.Thermal degradation of this new supramolecular compound is a two-step process in air. At first phthalic acid (47.4%) released up to 230°C, meanwhile it loses water and transforms into phthalic anhydride. In EGA-MS spectra, the characteristic fragments of water (m/z=17, 18) appear from about 180°C, while absorption bands of phthalic anhydride are shown in EGA-FTIR spectrum at about 210°C. In the second step theophylline begins to sublime, melts at 276°C, and then evaporates up to 315°C with minute residues.     

Identification of a new degradation product of the antifouling agent irgarol 1051 in natural samples

A main degradation product of Irgarol [2-(methylthio)-4-(tert-butylamino)-6-(cyclopropylamino)-s-triazine], one of the most widely used compounds in antifouling paints, was detected at trace levels in seawater and sediment samples collected from several marinas on the Mediterranean coast. This degradation product was identified as 2-methylthio-4-tert-butylamino-s-triazine. The unequivocal identification of this compound in seawater samples was carried out by solid-phase extraction (SPE) coupled on-line with liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS). SPE was carried out by passing 150 ml of seawater sample through a cartridge containing a polymeric phase (PLRP-s), with recoveries ranging from 92 to 108% (n=5). Using LC-MS detection in positive ion mode, useful structural information was obtained by increasing the fragmentor voltage, thus permitting the unequivocal identification of this compound in natural samples. Method detection limits were in the range of 0.002 to 0.005 microg/l. Overall, the combination of on-line SPE and LC-APCI-MS represents an important advance in environmental analysis of herbicide degradation products in seawater, since it demonstrates that trace amounts of new polar metabolites may be determined rapidly. This paper reports the LC-MS identification of the main degradation product of Irgarol in seawater and sediment samples.