Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LACTONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources
PubMed1990

Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A synthase by antibiotic 1233A and other beta-lactones.

3-Hydroxy-3-methylglutaryl CoA synthase was shown to be inhibited in a time-dependent, irreversible manner by compounds containing the substituted beta-lactone functionality found in the natural product 1233A. The rate of inactivation (kinact) was found to approach the rate of catalysis (kcat). The inactivation was irreversible over several hours. A related compound lacking the hydroxymethyl substituent on the beta-lactone ring is a reversible inhibitor and is competitive with respect to acetylCoA. The results are consistent with beta-lactone ring opening by the active site Cys to form an enzyme bound thioester.

Acetates↗
PubMed1991

Halo enol lactone inhibitors of chymotrypsin: burst kinetics and enantioselectivity of inactivation.

Burst kinetics in the inactivation of alpha-chymotrypsin by halo enol lactones 1 and 2 was observed. These results are consistent with a kinetic scheme that includes partitioning of the first acyl enzyme between transient inhibition and permanent inactivation. Partition ratios were estimated from the measured rates of the irreversible inactivation and the rates of deacylation of the second acyl enzyme. Halo enol lactones with a large burst resulted in small partition ratios, indicating a high potency of inactivation. We also observed enantioselectivity in the burst of inactivation such that the R enantiomer of lactone 1 showed a large burst, while the S enantiomer showed a little burst. This suggests that it is the R enantiomer whose binding is better suited for the covalent derivatization of the enzyme, or whose reactive halomethyl group is in an unfavorable position for the hydrolysis by water.

Amino Acid Sequence↗
PubMed1986

The effect of the sesquiterpene lactones from Geigeria on glycolytic enzymes.

The effect of sesquiterpene lactones isolated from Geigeria was tested on three glycolytic enzymes. Phosphofructokinase was inhibited irreversibly by all of the sesquiterpene lactones, with ivalin(III) giving the highest extent of inhibition. Values for the kinetic constants Ki (1.3 mM) and kp (2.2 min-1) were established. Hexokinase and glyceraldehyde-3-phosphate dehydrogenase were also strongly inhibited at 1 mM and 3 mM concentrations of sesquiterpene lactones, respectively. Pre-incubation of ivalin with dithiothreitol decreased its inhibiting effect on phosphofructokinase, hexokinase and glyceraldehyde-3-phosphate dehydrogenase activities. Phosphofructokinase and hexokinase were protected against inhibition by ivalin by their respective substrates, adenosine-5'-triphosphate and glucose.

Adenosine Triphosphate↗
PubMed1991

Aggregation properties of GD1b, II3Neu5Ac2GgOse4Cer, and of GD1b-lactone, II3[alpha-Neu5Ac-(2----8, 1----9)-alpha-Neu5Ac]GgOse4Cer, in aqueous solution.

The relevance of the presence of an inner ester in the oligosaccharide chain on the aggregative properties of gangliosides is investigated. Micellar molecular weight and hydrodynamic radius of natural GD1b and of semisynthetic GD1b-lactone are measured by the laser light scattering technique. The presence of the lactone ring causes an increase of 36% for the molecular weight and 16% for the hydrodynamic radius. Measurements on mixtures of GD1b and GD1b-lactone show that mixed micelles are formed with microdomain structure. The results are interpreted in terms of the geometrical packing model for the aggregation of amphiphilic molecules and are correlated to membrane processes.

Carbohydrate Sequence↗
PubMed1976

Simplified radioimmunoassay for aldosterone using antisera to aldosterone-gamma-lactone.

A simplified, non-chromatographic method for aldosterone-gamma-lactone (2) radio-immunoassay is described, using a high titer aldosterone-gamma-lactone antibody. This method takes six working hours for completion; the blanks are below the sensitivity of the assay (0-10 pg), and the intra and interassay coefficient of variation is 4.9% and 8.2% respectively. There is no significant variation with different plasma volumes assayed and the plot of added and assayed aldosterone gives a slope of 0.983. The negligible cross reactivity with other steroids and lactones eliminates the problem of interference by these substances.

Aldosterone↗
PubMed1994

Reversed-phase high-performance liquid chromatographic method for the simultaneous quantitation of the carboxylate and lactone forms of the camptothecin derivative irinotecan, CPT-11, and its metabolite SN-38 in plasma.

Irinotecan, also known as CPT-11 (I), is a potent semi-synthetic derivative of 20(S)-camptothecin (CPT). Like all known active derivatives of CPT, the lactone forms of I and its active metabolite SN-38 (II) are reversibly hydrolysed to inactive carboxylate forms. We describe a sensitive and selective HPLC method using the ion-pairing reagent tetrabutylammonium phosphate (TBAP) which allows the simultaneous determination of the carboxylate and lactone forms of I and II in human plasma samples following the precipitation of plasma proteins with an ice-cold mixture of acetonitrile and methanol. The mobile phase was 0.075 M ammonium acetate buffer (pH 6.4)-acetonitrile (78:22, v/v) containing 5 mM TBAP. Separation of the compounds was performed on a radially-compressed C18 column. The limits of quantitation in human plasma were 2 and 10 ng/ml for the two forms of II and I, respectively. In addition, we propose the use of CPT lactone both as an internal standard and as a "watchdog" for sample status. Under unsuitable storage conditions, CPT elutes increasingly in its carboxylate form thereby alerting the operator of possibly erroneous determinations of the concentrations of both forms of I and II. The retention times of the peaks of interest are well separated from the solvent front. This enables the detection of early eluting metabolites. The method was successfully used for monitoring of the two forms of I and II in patients treated with I.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Lactones of disialyl lactose: characterisation by NMR and mass spectra.

The lactonisation of alpha-Neup5Ac-(2-->8)-alpha-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-D-Glc (disialyl lactose) was investigated. (1)H and (13)C NMR chemical shifts of disialyl lactose and alpha-Neup5Ac-(2-->8, 1-->9)-alpha-Neup5Ac-(2-->3, 1-->2)-beta-D-Galp-(1-->4)-D-Glc (disialyl lactose-dilactone) were assigned based on 1D and 2D NMR results, including edited HSQC, HSQC-TOSCY and HMBC. The time course of lactonisation was followed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) with electrospray ionisation (ESI) mass spectrometry (MS) detection. The rate of lactonisation between alpha-(8)Neu5Ac and alpha-(3)Neu5Ac residues (lactonisation at the alpha-(2-->8) linkage) was faster than that of lactonisation between alpha-(3)Neu5Ac and Gal residues (lactonisation at the alpha-(2-->3) linkage). The mass spectra of disialyl lactose, its lactones, alpha-Neup5Ac-(2-->8)-alpha-Neup5Ac (alpha-(2-->8) disialic acid) and alpha-Neup5Ac-(2-->3)-beta-D-Galp-(1-->4)-D-Glc-lactone (3'-sialyllactose-lactone) showed that the alpha-(2-->8) linkage between Neu5Ac residues is difficult to cleave in the ESI-MS, compared with the alpha-(2-->3) linkage between Neu5Ac and Gal residues.

Animals↗
PubMed2006

Facile synthesis of a D-galactono-1,6-lactone derivative, a precursor of a copolyester.

2,3,4,6-Tetra-O-methyl-d-galactonic acid (5) was readily prepared from d-galactono-1,4-lactone (1) in 47% yield. The sequence involves tritylation of HO-6 of 1, followed by O-permethylation and deprotection. Lactonization of 5 led to the per-O-methyl-d-galactono-1,6-lactone, which was copolymerized with epsilon-caprolactone by ring-opening polymerization catalyzed by scandium triflate. The incorporation of the sugar comonomer into the polyester chain was about 10%.

Caproates↗
PubMed2004

Simple strategy for the optimization of solid-phase extraction procedures through the use of solid-liquid distribution coefficients application to the determination of aliphatic lactones in wine.

A practical strategy for the optimization of solid-phase extraction (SPE) systems is presented. Critical SPE volumes (sample loaded, rinsing and elution solvent) are calculated from solid-liquid extraction coefficients and from basic bed parameters determined in simple experiments, using the Lövkist Jonsson model and other expressions derived from the general theory of chromatography. The agreement between calculated and measured volumes is satisfactory, which makes it possible to consider different sorbents and rinsing and elution solvents in the SPE optimization with a relatively low experimental effort. The strategy has been successfully applied to the optimization of a SPE method directed to the selective extraction of aliphatic lactones from wine. Six different reversed-phase sorbents were studied and the one showing maximum extraction selectivity was selected. Wine (50 ml) is extracted in a 200 mg cartridge filled with Bond Elut-ENV resins. Interferences are removed with 20 ml of methanol-water (40:60) with 1% NaHCO3. Elution is carried out with 1.8 ml of dichloromethane. The extract is concentrated to 0.15 ml and analyzed by GC-ion trap MS. Eight odor-active aliphatic gamma and delta lactones (with 8-12 C atoms) from wine are recovered (R > 75%) in an extract free from wine major volatiles. Detection limits are in the 40-300 ng/l range, well below the odor detection threshold of these compounds. Linearity (r2 > 0.996) and precision (average R.S.D. 3.5%) are satisfactory in all cases. The levels in wine of some of these lactones (gamma-octa, undeca and dodecalactones) are reported by first time and results demonstrate that can be present at concentrations above or close to their corresponding odor thresholds.

Chromatography, Liquid↗
PubMed2004

Conformationally constrained diacylglycerol (DAG) analogs: 4-C-hydroxyethyl-5-O-acyl-2,3-dideoxy-D-glyceropentono-1,4-lactone analogs as protein kinase C (PKC) ligands.

The (R)-DAG-lactones (5 and 7E/Z) are conformationally constrained diacylglycerol (DAG) analogs with high potency as protein kinase C (PKC) ligands. Here, we have prepared and characterized their one-carbon lengthened analogs (6 and 8E/Z). The target compounds were synthesized from 1,2-O-isopropylidene D-xylose through a key intermediate, 4-C-hydroxyethyl-2,3-dideoxy-D-glyceropentono-1,4-lactone (13); they were evaluated as competitive ligands to displace bound [(3)H]phorbol 12,13-dibutyrate (PDBU) from a recombinant single isozyme (PKC-alpha). The binding affinities of the synthesized compounds were K(i) = 2.623 microM for 6, K(i) = 1.080 microM for 8Z and K(i) = 0.92 microM for 8E, which were ca. 27, 90, and 70 times less potent than the corresponding parent compounds (5, 7Z and 7E). Molecular modeling indicated that the reduced binding affinity of the representative 3-alkylidene lactone 8Z, as compared to 7Z, may be explained by its poor fit in the sn-1 binding mode as well as by its entropic loss due to the relatively flexible hydroxyethyl group.

Binding, Competitive↗
PubMed2005

Simple and sensitive high performance liquid chromatographic method for the simultaneous quantitation of the lactone and carboxylate forms of topotecan in human plasma.

A selective and highly sensitive isocratic high performance liquid chromatographic (HPLC) method is described for simultaneous determination of lactone and carboxylate species of topotecan, in plasma. The method utilizes a protein precipitation step with cold methanol (-20 degrees C) for sample preparation followed by separation on a Novapack C(18) column using ammonium acetate buffer, acetonitrile and triethylamine (84:16:1.5, v/v) containing tetrabutyl ammonium hydrogen sulfate (TBAHS) (2 mM) with a pH of 5 as the mobile phase. The eluted peaks were detected by a fluorescence detector was set at an excitation wavelength of 380 nm and an emission wavelength of 527 nm. The method was validated in the range of lactone and carboxylate forms of topotecan concentrations from 0.05 to 75 ng/ml. Intra- and inter-day precision expressed by the relative standard deviation was less than 8.50% and inaccuracy did not exceed 10% for lactone and carboxylate forms of topotecan. The limit of quantitation was 0.05 ng/ml using 0.50 ml plasma. Stability studies in plasma and plasma extract indicated that topotecan is stable for at least 2 weeks at -70 degrees C.

Carboxylic Acids↗
PubMed2005

Dual modes of modification of hepatitis A virus 3C protease by a serine-derived beta-lactone: selective crystallization and formation of a functional catalytic triad in the active site.

Hepatitis A virus (HAV) 3C proteinase is a member of the picornain cysteine proteases responsible for the processing of the viral polyprotein, a function essential for viral maturation and infectivity. This and its structural similarity to other 3C and 3C-like proteases make it an attractive target for the development of antiviral drugs. Previous solution NMR studies have shown that a Cys24Ser (C24S) variant of HAV 3C protein, which displays catalytic properties indistinguishable from the native enzyme, is irreversibly inactivated by N-benzyloxycarbonyl-l-serine-beta-lactone (1a) through alkylation of the sulfur atom at the active site Cys172. However, crystallization of an enzyme-inhibitor adduct from the reaction mixture followed by X-ray structural analysis shows only covalent modification of the epsilon2-nitrogen of the surface His102 by the beta-lactone with no reaction at Cys172. Re-examination of the heteronuclear multiple quantum coherence (HMQC) NMR spectra of the enzyme-inhibitor mixture indicates that dual modes of single covalent modification occur with a >/=3:1 ratio of S-alkylation of Cys172 to N-alkylation of His102. The latter product crystallizes readily, probably due to the interaction between the phenyl ring of the N-benzyloxycarbonyl (N-Cbz) moiety and a hydrophobic pocket of a neighboring protein molecule in the crystal. Furthermore, significant structural changes are observed in the active site of the 3C protease, which lead to the formation of a functional catalytic triad with Asp84 accepting one hydrogen bond from His44. Although the 3C protease modified at Cys172 is catalytically inactive, the singly modified His102 N(epsilon2)-alkylated protein displays a significant level of enzymatic activity, which can be further modified/inhibited by N-iodoacetyl-valine-phenylalanine-amide (IVF) (in solution and in crystal) or excessive amount of the same beta-lactone inhibitor (in solution). The success of soaking IVF into HAV 3C-1a crystals demonstrates the usefulness of this new crystal form in the study of enzyme-inhibitor interactions in the proteolytic active site.

3C Viral Proteases↗
PubMed2005

Structure of the Escherichia coli quorum sensing protein SdiA: activation of the folding switch by acyl homoserine lactones.

The three-dimensional structure of a complex between the N-terminal domain of the quorum sensing protein SdiA of Escherichia coli and a candidate autoinducer N-octanoyl-L-homoserine lactone (C8-HSL) has been calculated in solution from NMR data. The SdiA-HSL system shows the "folding switch" behavior that has been seen for quorum-sensing factors produced by other bacterial species. In the presence of C8-HSL, a significant proportion of the SdiA protein is produced in a folded, soluble form in an E.coli expression system, whereas in the absence of acyl homoserine lactones, the protein is expressed into insoluble inclusion bodies. In the three-dimensional structure, the autoinducer molecule is sequestered in a deep pocket in the hydrophobic core, forming an integral part of the core packing of the folded SdiA. The NMR spectra of the complex show that the bound C8-HSL is conformationally heterogeneous, either due to motion within the pocket or to heterogeneity of the bound structure. The C8-HSL conformation is defined by NOEs to the protein only at the terminal methyl group of the octanoyl chain. Unlike other well-studied bacterial quorum sensing systems such as LuxR of Vibrio fischeri and TraR of Agrobacterium tumefaciens, there is no endogenous autoinducer for SdiA in E.coli: the E.coli genome does not contain a gene analogous to the LuxI and TraI autoinducer synthetases. We show that two other homoserine lactone derivatives are also capable of acting as a folding-switch autoinducers for SdiA. The observed structural heterogeneity of the bound C8-HSL in the complex, together with the variety of autoinducer-type molecules that can apparently act as folding switches in this system, are consistent with the postulated biological function of the SdiA protein as a detector of the presence of other species of bacteria.

Amino Acid Sequence↗
PubMed2004

Anti-inflammatory and anti-hyperalgesic effects of sesquiterpene lactones from Magnolia and Bear's foot.

Sesquiterpene lactones possess a variety of biological activities, including anti-inflammatory activity. Two plants native to the southeastern United States, Magnolia grandiflora (L.) and Smallanthus uvedalius (L.) [syn Polymnia uvedalius (L.)], are novel sources of the sesquiterpene lactones parthenolide and enhydrin, respectively. In this study, the anti-inflammatory and anti-hyperalgesic effects of these isolated lactones from these two plant sources were evaluated in the rat carrageenan inflammation model. Rats received ip injections of either vehicle (propylene glycol), indomethacin (5 mg/kg), 11,13-dihydroparthenolide (20 mg/kg), parthenolide (5 or 20 mg/kg) or enhydrin (5 or 20 mg/kg). A 100-microl injection of 2.0% carrageenan was made into the plantar surface of the right hindpaw. Paw withdrawal latencies and paw volumes in both inflamed and non-inflamed paws were recorded at four test intervals: pre-inflammation baseline (0 time point), and 1, 2 and 4 h post-carrageenan injection. Vehicle-treated animals exhibited a significant time-dependent hyperalgesic and edema response that was greatest at the 4-h test interval. Indomethacin significantly blocked the hyperalgesic response and modestly attenuated the edema response. Parthenolide (20 mg/kg) and enhydrin (20 mg/kg) significantly blocked the hyperalgesic response and significantly attenuated the edema response; 11,13-dihydroparthenolide did not affect either inflammation or hyperalgesia. These findings suggest that parthenolide and enhydrin from these plant sources may be useful in the treatment of inflammatory pain.

Analgesics, Non-Narcotic↗
PubMed2005

The cytotoxicity of naturally occurring styryl lactones.

We extracted and isolated three natural styryl lactones from Goniothalamus griffithii Hook f. Thoms and investigated their cytotoxicity on a panel of three hepatocyte cell lines, HepG2, drug resistant HepG2 (HepG2-R) and primary cultured normal mice hepatocyte in order to find candidates of potential anti-cancer drugs which have low toxicity on normal cells and high effect on tumors or drug resistant tumors. All the three styryl lactones showed evident cytotoxic activities on both HepG2 and HepG2-R cell lines; however, gonithalamin and goniodiol shows less toxicity on normal mice hepatocyte as the IC(50) values of them on normal mice hepatocyte were about three times of that on HepG2. Morphological observation and cell cycle analysis were employed to elucidate the mechanisms of cytotoxicity of the tested compounds. Many apoptotic cells were observed in gonithalamin- and altholactone-treated cells, whereas, cells with chromosomes gathered at the equator were easily found in goniodiol-treated cultures. The analysis of cell cycle showed that G(2)/M arrest contributed to goniothalimin- and gonidiol-caused cell death and apoptosis was the cause of gonithalamin- and altholactone-induced cell death. Our results suggest that the three styryl lactones may be prospectively developed into anti-tumor drugs, especially on treating drug-resistance tumor after structure modification.

Animals↗
PubMed1982

Synthesis of L-idaro-1,4-lactone, an inhibitor of alpha-L-idosiduronase.

L-idaro-1,4-lactone was synthesized by two different, published methods: (1) epimerization of monopotassium D-glucarate by refluxing in aqueous barium hydroxide, and (2) oxidation of L-iditol by heating in dilute nitric acid. The lactone, formed by heat dehydration from aqueous solution at low pH, was purified by paper chromatography, and quantitated by gas-liquid chromatography using inositol as the internal standard. The monolactone inhibited human, seminal-fluid alpha-L-idosiduronase activity, with either phenyl or 4-methylumbelliferyl alpha-L-idosiduronic acid as the substrate, to the same degree as D-glucaro-1,4-lactone inhibits alpha-D-glucosiduronase.

Glucaric Acid↗
PubMed2002

An improved synthesis of 5-thio-D-ribose from D-ribono-1,4-lactone.

5-Thio-D-ribopyranose was synthesized from D-ribono-1,4-lactone (1) by two approaches: (i) 5-bromo-5-deoxy-D-ribono-1,4-lactone (2) was successively transformed into 5-bromo-5-deoxy, 5-S-acetyl-5-thio or 5-thiocyanato-D-ribofuranose derivatives; appropriate treatment then lead to 5-thio-D-ribopyranose (7) in 46-48% overall yield and; (ii) 2 was transformed into the 5-S-acetyl-5-thio-D-ribono-1,4-lactone derivative (11). Reduction and deprotection of 11 afforded 5-thio-D-ribopyranose (7) in 57% overall yield.

Lactones↗