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 919 records · Page 51Linked to original sources
PubMed2000

25-Dehydro-1alpha-hydroxyvitamin D3-26,23S-lactone antagonizes the nuclear vitamin D receptor by mediating a unique noncovalent conformational change.

(23S)-25-dehydro-1alpha-Dihydroxyvitamin D3-26,23-lactone (TEI-9647; MK) has been reported to antagonize the 1alpha,25-dihydroxyvitamin D3 nuclear receptor (VDR)- mediated increase in transcriptional activity. Using a transient transfection system incorporating the osteocalcin VDRE (vitamin D response element) in Cos-1 cells, we found that 20 nM MK antagonizes VDR-mediated transcription by 50% when driven by 1 nM 1alpha,25(OH)2D3. Four analogs of 1alpha,25(OH)2D3, also at 1 nM, were antagonized 25 to 39% by 20 nM MK. However, analogs with 16-ene/23-yne or 20-epi modifications, which have a significantly lower agonist ED50 for the VDR than 1alpha,25(OH)2D3, were antagonized by 20 nM MK only at 100 pM or 10 pM, respectively. One possible mechanism for antagonism is that the 25-dehydro alkene of MK might covalently bind the ligand-binding site of the VDR rendering it inactive. Utilization of a ligand exchange assay, however, demonstrated that MK bound to VDR is freely exchanged with 1alpha,25(OH)2D3 in vitro. These data support the apparent correlation between VDR transcriptional activation by agonists and the effective range of MK antagonism by competition. Furthermore, protease sensitivity analysis of MK bound to VDR indicates the presence of a unique conformational change in the VDR ligand-binding domain, showing a novel doublet of VDR fragments centered at 34 kDa, whereas 1alpha,25(OH)2D3 as a ligand produces only a single 34-kDa fragment. In comparison, the natural metabolite 1alpha,25-dihydroxyvitamin D3-26,23-lactone yields only the 30-kDa fragment that is produced by all ligands to varying degrees. Collectively, these results support that MK is a potent partial antagonist of the VDR for 1alpha,25(OH)2D3 and its analogs when in appropriate excess of the agonist.

Animals↗
PubMed2005

Active lactonizing lipase (LipL) efficiently overproduced by Pseudomonas strains as heterologous expression hosts.

Pseudomonas sp. strain 109 secretes lactonizing lipase (LipL), which catalyzes efficient intramolecular transesterification of omega-hydroxyfatty acid esters to form macrocyclic lactones. Because Escherichia coli was found to be unsuitable as an expression host due to the predominant formation of inactive LipL-inclusion bodies and a lack of proper secretion machinery which is also required for the formation of active LipL, Pseudomonas strains were surveyed as expression hosts. Pseudomonas sp. strain 109, an original LipL producer, showed a 7.1-fold higher level of active LipL when the lipL gene under the control of tac-lacUV5 tandem promoter was introduced together with a limL gene encoding a LipL-specific chaperon. Pseudomonas aeruginosa ADD 1976 containing a T7 RNA polymerase gene in the chromosome and plasmid-borne lipL-limL genes under the control of T7 promoter showed a 13-fold higher level of active LipL. Several combinations in the number of lipL and/or limL genes on the plasmid were investigated, and (lipL)3-limL was found to be most efficient, yielding a 67-fold greater production of active LipL than that obtained by the wild-type Pseudomonas sp. strain 109.

Bacterial Proteins↗
PubMed1989

Behavior of 3,4-endiol form of 2,3-diketo-gulono-delta-lactone formed from dehydro-L-ascorbic acid in deoxygenated and neutral solution.

The formation of L-ascorbic acid (AsA) was observed when dehydro-L-ascorbic acid (DHA) was dissolved in neutral buffer solutions under N2 bubbling at room temperature. The reduction of DHA was done with the lactonized compound of 2,3-diketo-L-gulonic acid (DKG), that is, the 3,4-endiol form of 2,3-diketo-gulono-delta-lactone (3,4-End DKGL). 3,4-End DKGL was formed from DHA or DKG (yield about 10%) under N2 bubbling in neutral buffer solution (pH 7.2). This material was not stable in neutral or alkaline solutions. 3,4-End DKGL suppressed more strongly the linoleic acid (LA) peroxidation in the medium containing 20% EtOH and 10 mM LA than did AsA. This may suggest the possibility that 3,4-End DKGL reproduces AsA from DHA in physiological status.

2,3-Diketogulonic Acid↗
PubMed2002

The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation.

Pseudomonas aeruginosa causes lethal lung infections in immunocompromised individuals such as those with cystic fibrosis. The lethality of these infections is directly associated with inflammation and lung tissue destruction. P. aeruginosa produces several acylated homoserine lactones (AHL) that are important in the regulation of bacterial virulence factors. Little is known about the effects of AHLs on human cells. In this work we report that the AHL N-(3-oxododecanoyl) homoserine lactone (3O-C(12)-HSL) from P. aeruginosa induces cyclooxygenase (Cox)-2, a seminal proinflammatory enzyme. When primary normal human lung fibroblasts were exposed to 3O-C(12)-HSL, an 8-fold induction in mRNA and a 35-fold increase in protein for Cox-2 were observed. In contrast, there was no substantial change in the expression of Cox-1. We also demonstrated that the induction of Cox-2 was regulated by 3O-C(12)-HSL activation of the transcription factor NF-kappaB. 3O-C(12)-HSL also stimulated an increase in the newly discovered inducible membrane-associated PGE synthase but had no effect on the expression of the cytosolic PGE synthase. We also demonstrate that 3O-C(12)-HSL stimulated the production of PGE(2). PGE(2) is known to induce mucus secretion, vasodilation, and edema, and acts as an immunomodulatory lipid mediator. We propose that 3O-C(12)-HSL induction of Cox-2, membrane-associated PGE synthase, and PGE(2) likely contributes to the inflammation and lung pathology induced by P. aeruginosa infections in the lung. These studies further reinforce the concept that bacterial AHLs not only regulate bacterial virulence but also stimulate the activities of eukaryotic cells important for inflammation and immune defenses.

4-Butyrolactone↗
PubMed1999

The antiinflammatory sesquiterpene lactone parthenolide inhibits NF-kappa B by targeting the I kappa B kinase complex.

The transcription factor NF-kappa B is a key regulator of the cellular inflammatory and immune response. Therefore, components of the NF-kappa B-activating signaling pathways are frequent targets for antiinflammatory agents. This study shows that the sesquiterpene lactone parthenolide inhibits a common step in NF-kappa B activation by preventing the TNF-alpha-induced induction of I kappa B kinase (IKK) and IKK beta, without affecting the activation of p38 and c-Jun N-terminal kinase. Parthenolide impairs NF-kappa B-dependent transcription triggered by expression of TNFR-associated factor-2, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEKK1), and NF-kappa B-inducing kinase. This compound also prevents activation of both IKKs and DNA binding of NF-kappa B induced by MEKK and NF-kappa B-inducing kinase. Parthenolide targets a component of the I kappa B kinase complex without directly inhibiting IKK alpha, IKK beta, or MEKK1. Therefore, this sesquiterpene lactone could serve as a lead compound for the development of antiinflammatory remedies and is suitable as a molecular tool, allowing the dissection of TNF-alpha-derived signaling pathways leading to the activation of NF-kappa B, c-Jun N-terminal kinase, and p38.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

[The effect of sclareol lactone and sclareol glycol on artificially induced lung metastases of Lewis lung carcinoma (a preliminary report)].

The prophylactic effect of tetralabdanes, obtained by chemical decomposition of the natural diterpene sclareol (Il. Ognianov and T. Somleva) on the growth of artificially induced lung metastases was studied. After intravenous administration of 25 mg/kg of sclareol-lacton 30 minutes before the transplantation of tumorous cells of Lewis [correction of Luis] lung carcinoma the number of metastases was reduced with 37.5% but in a dose of 50 mg/kg from--33 to 63%. In a dose of 100 mg/kg of sclareol-lacton metastases were increased with 2--7%. Sclareolglycol administered in a dose of 25 mg/kg under the same experimental conditions, reduced lung metastases with 38%, but in a dose of 50 mg/kg--from 26% to 61%. Its administration in a dose of 100 mg/kg stimulated their formation with 62%.

Animals↗
PubMed1989

[Synthesis and study of the convulsant action of polycyclic amino-gamma-lactone and of its tetrahydrofuran analogue].

In this paper, the synthesis of the gamma-benzyl-amino-gamma-lactone 6 and its tetrahydrofuran analogue 8 is described. Their convulsant action was studied in mice. They display a weak convulsant activity coming with sedation and myorelaxation. The introduction of the benzyl group abolishes the strong convulsant and lethal action characteristic of the already studied non benzylated aminolactones but leaves intact the aminoethers activity. These results could indicate that the activity of these amino-gamma-lactones is essentially antiglycinergic and those of the corresponding aminoethers is anti-GABAergic lined with a partial agonist action.

Animals↗
PubMed1988

L-gulono-gamma-lactone oxidase deficiency in rats with osteogenic disorder: enzymological and immunochemical studies.

A strain of Wistar rats with L-gulono-gamma-lactone oxidase deficiency has recently been established. The activity of L-gulono-gamma-lactone oxidase in hepatic microsomes of the mutant rats was not detectable, while that of heterozygous rats was about half that of normal rats. These results were confirmed by immunological quantitation using antibody directed against this enzyme. Thus, it appears that these mutant rats either possess no enzyme at all or a very aberrant form of the enzyme in the liver. Aldonolactonase, another enzyme participating in the biosynthesis of L-ascorbic acid, was found to be present in normal amount in the mutant strain.

Animals↗
PubMed1981

The effect of sesquiterpene lactones on the synthesis of nucleic acid in cultures of human lymphocytes stimulated by phytohemagglutinin.

The investigated sesquiterpene lactones--alatolide, eupatoriopicrine and hydroxyisonobiline, at the concentration 5 microgram/ml, resulted in a complete inhibition of 3H-uridine incorporation into RNA and 3H-thymidine into DNA in cultures of human lymphocytes stimulated by PHA. The blast and mitotic index was close or equal to 0 at this concentration of substances. Susceptibility to the investigated lactones was highest at the initial stage of lymphocyte culture and it gradually decreased with the progression of blastic transformation. At the stage of advanced RNA and DNA synthesis, an addition of the substances to cultures was without any inhibitory effect on the synthesis process.

DNA↗
PubMed1983

Contact allergy to parthenolide in Tanacetum parthenium (L.) Schulz-Bip. (feverfew, Asteraceae) and cross-reactions to related sesquiterpene lactone containing Compositae species.

A case of specific, delayed hypersensitivity induced by repeated contact with a wild form of feverfew (Tanacetum parthenium) is reported. In the flowers investigated the content of the responsible contact allergen parthenolide--a potent sesquiterpene lactone--appeared to be 10 times greater (0.6-0.9%) than in earlier years. Guinea pig experiments confirm the strong sensitizing potency of this Compositae species. Cross-reactions were elicited with 11 of 21 mostly Compositae plants containing chemically related sesquiterpene lactones. The strongest reactions were elicited by tansy, yarrow (milfoil), marguerite, aster, sunflower, laurel and Frullania. Structure elucidation by X-ray crystallographic analysis established the precise molecule configuration of parthenolide, although the lattice parameters of the isolated compound were not in accordance with those published in the literature.

Animals↗
PubMed1980

Synthesis and mutagenicity of 4-(N-butylnitrosamino)-4-hydroxybutyric acid lactone, a possible activated metabolite of the proximate bladder carcinogen N-butyl-N-(3-carboxypropyl)nitrosamine.

4-(N-Butylnitrosamino)-4-hydroxybutyric acid lactone (BBAL) was synthesized as a possible intermediate produced by metabolic activation of a selective bladder carcinogen, N-butyl-N-(3-carboxypropyl)nitrosamine. BBAL was stable in neutral sodium phosphate buffer (ionic strength, 0.2), having a half-life of more than 30 hr at 25 degrees. The mutagenic effects of BBAL were tested with the use of Salmonella typhimurium TA1535 and Escherichia coli B/rWP2-try-, WP2-try-hcr-, and Sd4. The gene-damaging effects were assayed by repair tests with Bacillus subtilis H17 (rec+) and M45 (rec-). BBAL showed potent effects in the mutation and repair tests on all the strains tested without activation. A possibility is suggested for the metabolic activation of N-butyl-N-(3-carboxypropyl)nitrosamine to BBAL by alpha-hydroxylation at the site of the 3-carboxypropyl chain followed by lactonization in target tissues prior to interaction with macromolecules to lead to carcinogenesis.

Bacillus subtilis↗
PubMed1983

The effect of sesquiterpene lactones, eupatoriopicrin and hydroxyisonobilin, on the glycolytic metabolism of human lymphocytes.

The effect of two sesquiterpene lactones of the germacranolide group, eupatoriopicrin and hydroxyisonobilin, on the glycolytic metabolism of human lymphocytes stimulated by phytohemagglutinin was tested. Glucose and lactic acid levels as well as the activities of phosphofructokinase, glyceraldehyde 3-phosphate dehydrogenase, pyruvate kinase, and lactate dehydrogenase were measured. Both lactones caused a decrease in glucose consumption and lactic acid formation as well as the inhibition of the tested enzymes. A stronger inhibitory effect was observed in the case of hydroxyisonobilin, particularly with regard to phosphofructokinase and glyceraldehyde 3-phosphate dehydrogenase.

Antineoplastic Agents↗
PubMed1982

Haloenol lactones: enzyme-activated irreversible inactivators for serine proteases. Inactivation of alpha-chymotrypsin.

Two haloenol lactones have been shown to inactivate alpha-chymotrypsin by an enzyme-mediated process. According to the postulated mechanism, acylation of the active site serine by the haloenol lactone reveals an alpha-haloketone, which alkylates the enzyme at the active site and renders the enzyme inactive. The inactivation has been shown to require enzymatic activation of the inhibitor to its reactive form to take place within the acyl-enzyme intermediate and to be irreversible.

Benzene Derivatives↗
PubMed1994

6-Allyl-5,6-dihydro-5-hydroxypyran-2-one, a lactone produced by a new Drechslera species: specified 1H and 13C NMR assignments, mutagenic and immunomodulating testings.

A lactone (6-allyl-5,6-dihydro-5-hydroxypyran-2-one) was isolated from a new Drechslera sp. 1H and 13C NMR assignments, not previously specified, are published. No mutagenic activity on Ames/Salmonella test (strains TA98 and TA100 has been observed. Results on the respiratory metabolism of J774.1 murine macrophage indicate that the lactone might exhibit immunomodulating activity as a function of time of cellular contact and of concentration.

Adjuvants, Immunologic↗
PubMed1994

Production by a baculovirus expression system of the APO-protein of L-gulono-gamma-lactone oxidase, a flavoenzyme possessing a covalently-bound FAD.

L-Gulono-gamma-lactone oxidase, an enzyme functioning in L-ascorbic acid biosynthesis in higher animals, possesses a covalently-bound FAD as the prosthetic group. Catalytically-active enzyme was expressed in silkworm cells by a recombinant baculovirus encoding rat L-gulono-gamma-lactone oxidase. When recombinant enzyme was expressed under riboflavin-deficient conditions, most of it was found to be the apoprotein, as evidenced by an increase in enzymic activity upon addition of FAD to the assay mixture. Interestingly, the observed enzymic activity is thought to have been provoked by a noncovalent interaction between FAD and the apoprotein, since the covalent attachment of FAD was not demonstrated by a fluorometric gel-scanning experiment.

Animals↗
PubMed1994

Biosynthesis of poly-3-hydroxybutyrate in the luminescent bacterium, Vibrio harveyi, and regulation by the lux autoinducer, N-(3-hydroxybutanoyl)homoserine lactone.

Poly-3-hydroxybutyrate (PHB), a biopolymer of important commercial applications, is found in a wide range of Gram-negative and Gram-positive bacteria and cyanobacteria. The present study has resulted in the identification of PHB in the luminescent marine bacteria, Vibrio harveyi, in spite of it being previously classified as PHB-negative. PHB granules with distinct membranes were detected by electron microscopy after fixation and staining of V. harveyi cells with malachite green. Analyses by gas chromatography, nuclear magnetic resonance, infrared, and ultraviolet spectroscopy clearly established the presence of PHB. The synthesis of PHB in V. harveyi was found to be under cell density regulation with the levels increasing from 0 (< 0.2) to 26 mg of PHB/g of dry cell weight during growth in a manner analogous to the induction of luminescence in this bacteria. Moreover, synthesis of PHB in V. harveyi was shown to be controlled by the lux autoinducer, N-(3-hydroxybutanoyl)homoserine lactone, providing not only a potential link between luminescence and PHB production but also showing that the lux autoinducer acts as a general signal transductant. These results have also extended the role of homoserine lactones in metabolic regulation to include the control of synthesis of potential energy reserves.

4-Butyrolactone↗
PubMed2000

Amphipathic structure of theonellapeptolide-Id, a hydrophobic tridecapeptide lactone from the Okinawa marine sponge Theonella swinhoei.

Theonellapeptolide-Id (TNLP), a cyclic tridecapeptide lactone, was crystallized from dimethylformamide-water solution. In the asymmetric unit, two peptide molecules were combined with solvent molecules, and the total molecular weight was over 3000 Dalton. The crystal structure including solvent molecules was finally determined at 0.80 A resolution using synchrotron radiation. The conformations of two independent molecules were similar to each other and were also similar to the previously reported structure (Doi, Ishida, Kobayashi, Deschamps and Flippen-Anderson, 1999, Acta Crystallogr Sect C, 55, 796-798). About 13 hydrated water molecules were found at disordered 19 sites; they were located at a certain region to avoid contact with aliphatic side-chains of peptolide in the crystal. The spatial disposition of the solvent molecules and peptides subsequently caused the formation of the amphipathic layer.

Animals↗