6-Aminohexanoic acid as a chemical chaperone for apolipoprotein(a). (1/259)
Apolipoprotein (a) (apo(a)) is a component of the atherogenic lipoprotein, Lp(a). The efficiency with which apo(a) escapes the endoplasmic reticulum (ER) and is secreted by the liver is a major determinant of plasma Lp(a) levels. Apo(a) contains a series of domains homologous to plasminogen kringle (K) 4, each of which possesses a potential lysine-binding site. By using primary mouse hepatocytes expressing a 17K4 human apo(a) protein, we found that high concentrations (25-200 mM) of the lysine analog, 6-aminohexanoic acid (6AHA), increased apo(a) secretion 8-14-fold. This was accompanied by a decrease in apo(a) presecretory degradation. 6AHA inhibited accumulation of apo(a) in the ER induced by the proteasome inhibitor, lactacystin. Thus, 6AHA appeared to inhibit degradation by increasing apo(a) export from the ER. Significantly, 6AHA overcame the block in apo(a) secretion induced by the ER glucosidase inhibitor, castanospermine. 6AHA may therefore circumvent the requirement for calnexin and calreticulin interaction in apo(a) secretion. Sucrose gradients and a gel-based folding assay were unable to detect any influence of 6AHA on apo(a) folding. However, non-covalent or small, disulfide-dependent changes in apo(a) conformation would not be detected in these assays. Proline also increased the efficiency of apo(a) secretion. We propose that 6AHA and proline can act as chemical chaperones for apo(a). (+info)Suppression of murine endotoxic shock by sPLA2 inhibitor, indoxam, through group IIA sPLA2-independent mechanisms. (2/259)
Endotoxic shock is a systemic inflammatory process, involving a variety of proinflammatory mediators. Two types of secretory phospholipase A2 (sPLA2) have been implicated in this process. Group IB sPLA2 (PLA2-IB) binds to the PLA2 receptor (PLA2R), and PLA2R-deficient mice exhibit resistance to endotoxin-induced lethality with reduced plasma levels of proinflammatory cytokines, such as TNF-alpha. Group IIA sPLA2 (PLA2-IIA) is found in many tissues and cell types, and local and systemic levels are elevated under numerous inflammatory conditions including sepsis. In this study, we investigated the effect of a specific sPLA2 inhibitor, indoxam, on murine endotoxic shock. Indoxam suppressed the elevation of plasma TNF-alpha with a similar potency in PLA2-IIA-expressing and PLA2-IIA-deficient mice after LPS challenge. In PLA2-IIA-deficient mice, indoxam also suppressed the elevation of plasma IL-1beta, IL-6 and NO, and prolonged survival after LPS challenge. Indoxam was found to block the PLA2-IB binding to murine PLA2R with a high potency (Ki=30 nM). The inhibitory effects of indoxam on the LPS-induced elevation of plasma TNF-alpha levels could not be observed in mice deficient in PLA2R. These findings suggest that indoxam blocks the production of proinflammatory cytokines during endotoxemia through PLA2-IIA-independent mechanisms, possibly via blockade of the PLA2R function. (+info)Use of inhibitors to characterize intermediates in the processing of N-glycans synthesized by insect cells: a metabolic study with Sf9 cell line. (3/259)
The most frequent type of N-glycan synthesized by lepidopteran Sf9 cells appears to be fucosylated Man3GlcNAc2,and this has been a limitation for a large scale production and utilization of therapeutic glycoproteins in cultured insect cells. The current knowledge of the protein glycosylation pathway derived from structural studies on recombinant glyco-proteins expressed by using baculovirus vectors. In this work we provide more direct evidence for the sequential events occurring in the processing of endogenous N-glycoproteins of noninfected Sf9 cells. By metabolic labeling with radioactive mannose, we characterized the glycan structures which accumulated in the presence of processing inhibitors (castanospermine and swainsonine) and in the presence of an intracellular trafficking inhibitor (monensin). We thus demonstrated that from the glycan precursor Glc3Man9GlcNAc2 to GlcNAcMan5(Fuc)GlcNAc2 intermediate, the processing pathway in Sf9 cells paralleled the one demonstrated in mammalian cells. By using monensin, we demonstrated the formation of Man3(Fuc)GlcNAc2 from GlcNAcMan3(Fuc)GlcNAc2, a reaction which has not been described in mammalian cells. Our results support the idea that the hexosaminidase activity is of physiological relevance to the glycosylation pathway and is Golgi located. (+info)High-mannose type oligosaccharide-dependent apoptosis in U937 cells induced by pradimicin, a mannose-binding antibiotic. (4/259)
Cell surface oligosaccharides play a role in a variety of biological events such as cell adhesion and signal transduction. We have shown that BMY-28864, a semi-synthetic analog of pradimicin, induced apoptosis of U937 cells which had been incubated with 1-deoxymannojirimycin, an inhibitor of mannosidase I. BMY-28864 was not cytotoxic to the cells which had been cultivated with other glycosidase inhibitors such as castanospermine and swainsonine. We thus propose that BMY-28864 induces apoptosis by acting on a specific mannose-rich oligosaccharide, presumably (Man)9(GlcNAc)2+. (+info)Differential role of mannose and glucose trimming in the ER degradation of asialoglycoprotein receptor subunits. (5/259)
To gain insight into how sugar chain processing events modulate endoplasmic reticulum (ER)/proteasomal degradation we looked at human asialoglycoprotein receptor polypeptides H2a and H2b, variants which differ only by an extra pentapeptide (EGHRG) present in H2a. Membrane-bound H2a is a precursor of a soluble secreted form while H2b reaches the plasma membrane. Uncleaved precursor H2a molecules are completely retained in the ER and degraded as well as a portion of H2b. Inhibition of N-linked sugar chain mannose trimming stabilized both variants. In contrast, inhibition of glucose trimming with castanospermine greatly enhanced the degradation rate of H2a but not that of H2b. We studied a possible involvement of the ER chaperone calnexin, as inhibitors of glucose trimming are known to prevent calnexin binding. Incubation of cells with low concentrations of castanospermine (30 microg/ml) did not interfere with calnexin binding to H2a while causing the same accelerated degradation as high concentrations (>100 microg/ml) which did inhibit the association. Castanospermine treatment after calnexin binding blocked the dissociation of the chaperone but still caused accelerated degradation. The increased degradation could be blocked by a specific proteasome inhibitor, ZL(3)VS. Our results suggest that extensive mannose trimming or retention of glucose residues due to lack of glucose trimming are signals for ER/proteasomal degradation independent of interaction with calnexin. (+info)Analysis of the early biogenesis of CD1b: involvement of the chaperones calnexin and calreticulin, the proteasome and beta(2)-microglobulin. (6/259)
beta(2)-Microglobulin (beta(2)m)-associated human CD1b proteins present lipid and glycolipid antigens, which are loaded on CD1b in endosomal compartments. In contrast, the related MHC class I molecules acquire antigenic peptides in the endoplasmic reticulum. Here, we investigated the biogenesis of CD1b before beta(2)m binding in comparison to MHC class I. In beta(2)m-deficient FO-1 cells, we found CD1b heavy chains (HC) complexed with the chaperones calnexin and calreticulin, while MHC class I HC associated only with calnexin. Despite this difference, both CD1b HC and MHC class I HC were degraded when the chaperone interactions were prevented by the glucosidase inhibitor castanospermine. The degradation of both molecules included the proteasome and mannosidases. Chaperone-unassociated CD1b could be rescued from degradation by supplementing FO-1 cells with beta(2)m. Finally, prevention of chaperone interaction significantly reduced neoexpression of CD1b upon differentiation of monocytes to dendritic cells, underlining the importance of chaperones for proper expression of CD1b under physiological conditions. (+info)Kinetics of interactions of sendai virus envelope glycoproteins, F and HN, with endoplasmic reticulum-resident molecular chaperones, BiP, calnexin, and calreticulin. (7/259)
Sendai virus envelope glycoproteins, F and HN, mature during their transport through the endoplasmic reticulum (ER) and Golgi complex. To better understand their maturation processes in the ER, we investigated the time course of their interactions with three ER- resident molecular chaperones, BiP, calnexin (CNX), and calreticulin (CRT), in Sendai virus-infected HeLa cells. Pulse-chase and immunoprecipitation analyses using antibodies against each virus glycoprotein or ER chaperone revealed that F precursor interacted with CNX transiently (t(1/2)=8 min), while HN protein displayed longer and sequential interactions with BiP (t(1/2)=8 min), CNX (t(1/2)=15 min), and CRT (t(1/2)=20 min). HN interacted with the three ER chaperones not only as a monomer but also as a tetramer for several hours, suggesting mechanism(s) to undergo chaperone-mediated quality control of an assembled HN oligomer in the ER. The kinetics of dissociation of the HN-chaperone complexes exhibited a marked delay in the presence of proteasome inhibitors, suggesting that a part of HN associated with BiP, CNX, and CRT is destined to be degraded in the proteasome-dependent pathway. Further, the associations between virus glycoproteins and CNX or CRT were impaired by castanospermine, an inhibitor of ER glucosidase I and II, confirming that these interactions require monoglucosylated oligosaccharide on F(0) and HN peptides. These findings together suggest that newly synthesized F protein undergoes rapid maturation in the ER through a transient interaction with CNX, whereas HN protein requires more complex processes involving prolonged association with BiP, CNX, and CRT for its quality control in the ER. (+info)Alpha-glucosidase inhibitors reduce dengue virus production by affecting the initial steps of virion morphogenesis in the endoplasmic reticulum. (8/259)
We report that endoplasmic reticulum alpha-glucosidase inhibitors have antiviral effects on dengue (DEN) virus. We found that glucosidase inhibition strongly affects productive folding pathways of the envelope glycoproteins prM (the intracellular glycosylated precursor of M [membrane protein]) and E (envelope protein): the proper folding of prM bearing unprocessed N-linked oligosaccharide is inefficient, and this causes delayed formation of prME heterodimer. The complexes formed between incompletely folded prM and E appear to be unstable, leading to a nonproductive pathway. Inhibition of alpha-glucosidase-mediated N-linked oligosaccharide trimming may thus prevent the assembly of DEN virus by affecting the early stages of envelope glycoprotein processing. (+info)Indolizines are organic compounds that consist of a condensed pyridine and pyrrole ring structure, which can be found in certain natural and synthetic substances, and have been studied for their potential biological activities.
I'm sorry for any confusion, but "Indolizines" is not a medical term. It is a chemical term that refers to a class of heterocyclic organic compounds which contain a seven-membered ring with two nitrogen atoms and a carbon-carbon double bond. They are used in the synthesis of various pharmaceuticals and natural products, but they are not a medical condition or diagnosis.
Indolizine
... is an heterocyclic compound with the formula C8H7N). It is an uncommon isomer of indole with the nitrogen located at ... Chemical synthesis of indolizines v t e (Articles without KEGG source, ECHA InfoCard ID from Wikidata, Articles containing ... ISBN 978-0-85404-182-4. Elattar, K.M.; Youssef, I.; Fadda, A.A. (4 May 2016). "Reactivity of indolizines in organic synthesis ... Indolizines, All stub articles, Heterocyclic compound stubs). ...
NNC 45-0095
February 2000). "Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non- ... Sharma V, Kumar V (2014). "Indolizine: a biologically active moiety". Medicinal Chemistry Research. 23 (8): 3593-3606. doi: ... Indolizines, Phenols, Pyrroles, Selective estrogen receptor modulators, All stub articles, Genito-urinary system drug stubs). ...
Indolizidine
Indole Indolizine Tryptophan Tryptamine Skvortsov, I. M.; Zadumina, E. A.; Ponomarev, A. A. (1965). "1-Azabicycles. IV. ...
5-Aza-7-deazapurine
Base analog Indolizine Purine analogue Seela, Frank; Amberg, Stefan; Melenewski, Alexander; Rosemeyer, Helmut (20 August 2001 ...
Davis-Beirut reaction
1. Indazole and indolizine-3-carboxylic acid derivatives". Journal of Medicinal Chemistry. 33 (7): 1924-1929. doi:10.1021/ ...
Photooxygenation
Li, Yun; H. Hu; J. Ye; H. Fun; H. Hu; J. Xu (2004). "Reaction modes and mechanism in indolizine photooxygenation reactions". ... Photooxygenation of indolizines (heterocyclic aromatic derivates of indole) has been investigated in both mechanistic and ... Note that the reaction proceeds through an indolizine radical cation intermediate that has not been isolated (and thus is not ... leading to the reaction of an indolizine derivative with the superoxide anion radical. ...
Oophaga sylvatica
Amongst the toxins found in O. sylvatica are histrionicotoxins, indolizines, lehmizidines, and decahydroquinolines. The toxins ...
Alexandru Balaban
In addition, he had been exploring new syntheses of indolizines and of naphthalene derivatives. In order to explain the ...
Coniine
A synthesis of the alkaloid, starting from indolizine (pyrrocoline) is described by Ochiai and Tsuda. The preparation of L-(R)- ... This, on hydrolysis and decarboxylation, furnishes indolizine, the octahydro-derivate of which, also known as ... which on oxidation with dilute nitric acid is converted into trimethyl indolizine-tricarboxylate. ...
Fantofarone
Indolizines, Phenol ethers, Isopropyl compounds). ...
Astragalus mongholicus
While several other species of Astragalus are known to cause severe poisonings in livestock due to indolizine alkaloids, ...
C8H7N
Indole Indolizine Isoindole This set index page lists chemical structure articles associated with the same molecular formula. ...
Pandanus utilis
... Growth habit Foliage Fruit Aerial roots Roots In Brazil Leaves Garden plant in Florida Stem Roots Indolizine ...
Indolizine - Wikipedia
Indolizine is an heterocyclic compound with the formula C8H7N). It is an uncommon isomer of indole with the nitrogen located at ... Chemical synthesis of indolizines v t e (Articles without KEGG source, ECHA InfoCard ID from Wikidata, Articles containing ... ISBN 978-0-85404-182-4. Elattar, K.M.; Youssef, I.; Fadda, A.A. (4 May 2016). "Reactivity of indolizines in organic synthesis ... Indolizines, All stub articles, Heterocyclic compound stubs). ...
Conformational equilibria and barriers to rotation in some novel nitroso derivatives of indolizines and 3- and 5-azaindolizines...
Conformational equilibria in novel C-nitroso derivatives of indolizines and 3- and 5-azaindolizines have been studied by NMR. ... derivatives of indolizines and 3- and 5-azaindolizines - an NMR. and molecular modeling study I. Ghiviriga, B. E. M. El-Gendy, ... indolizine. . Ethyl 2-(methylamino)-1-nitrosoindolizine-3-carboxylate. displayed conformers arising from the restricted ... Conformational equilibria in novel C-nitroso derivatives of indolizines and 3- and 5-azaindolizines have been studied by NMR. ...
IUCr) Structural investigation of methyl 3-(4-fluoro-benzo-yl)-7-methyl-2-phenyl-indolizine-1-carboxyl-ate, an inhibitory drug...
Transition-metal-free synthesis of indolizines via [3 + 2]-annulation from α-bromoenals and 2-substituted azaarenes<...
Liu, Y., Yu, Y., Fu, Y., Liu, Y., Shi, L., Li, H., & Wang, W. (2017). Transition-metal-free synthesis of indolizines via [3 + 2 ... Liu, Y, Yu, Y, Fu, Y, Liu, Y, Shi, L, Li, H & Wang, W 2017, Transition-metal-free synthesis of indolizines via [3 + 2]- ... Dive into the research topics of Transition-metal-free synthesis of indolizines via [3 + 2]-annulation from α-bromoenals and 2 ... Transition-metal-free synthesis of indolizines via [3 + 2]-annulation from α-bromoenals and 2-substituted azaarenes. Organic ...
Zeitschrift für Naturforschung B Volume 70 Issue 12
110351-94-5 (S)-4-ETHYL-4-HYDROXY-7,8-DIHYDRO-1H-PYRANO[3,4-F]INDOLIZINE-3,6,10(4H)-TRIONE - Watsonnoke Scientific Ltd
S)-4-hydroxy-4-propyl-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3. (S)-4-hydroxy-4-propyl-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3 ... You are here: Home / Products / Caming Pharmaceutical Ltd / (S)-4-ETHYL-4-HYDROXY-7,8-DIHYDRO-1H-PYRANO[3,4-F]INDOLIZINE-3,6,10 ... 4S)-4-ETHYL-4-HYDROXY-1H,3H,4H,6H,7H,8H,10H-PYRANO[3,4-F]INDOLIZINE-3,6,10-TRIONE. (4S)-4-ETHYL-4-HYDROXY-1H,7H,8H-PYRANO[3,4-F ... INDOLIZINE-3,6,10-TRIONE. (4S)-4-ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10-trione. (4S)-4-ethyl-7,8-dihydro ...
Staff listing - The University of Nottingham
staff directory entries | Idaho State University
CAS # 14174-98-2, 1,2-Indolizinedicarboxylicacid 1,2-Diethyl Ester: more information.
Publications | Life Sciences Institute
Symmetry | August 2019 - Browse Articles
HeteroCycles
Design of new cognition enhancers: from computer prediction to synthesis and biological evaluation - SciPeople
CCCC 1978, Volume 43, Issue 6, Abstracts pp. 1618-1627, Articles by the same authors | Collection of Czechoslovak Chemical...
Indolizidines (definition)
CCCC 1982, Volume 47, Issue 2, Abstracts pp. 523-534, Articles by the same authors | Collection of Czechoslovak Chemical...
Bioactivity evaluations of leaf extract fractions from young barley grass and correlation with their phytochemical profiles |...
For ex, Indolizine has anti-inflammatory properties [37]. Phytol is a diterpene which is reported to have anti-inflammatory and ... The GC-MS analysis of methanolic extract reported several phytoconstituents with anti-inflammatory activity such as Indolizine ... 5; Table 5). The major phytocomponents reported are Indolizine (21.78%), Octadecyl trifluoroacetate (15.85%), Palmitic acid ( ... Design, synthesis, and biological evaluation of some novel indolizine derivatives as dual cyclooxygenase and lipoxygenase ...
HeteroCycles
Search Results | DrugBank Online
Acyclic Nitrogen Containing Patents and Patent Applications (Class 544/119) - Justia Patents Search
Chalcogen Attached Indirectly To The Six-membered Hetero Ring By Nonionic Bonding Patents and Patent Applications (Class 546...
Yang Zhang
Bead tree - Medicinal Plants : Medicinal Plants
Quinolizines | Harvard Catalyst Profiles | Harvard Catalyst
基于<i>D</i>...
Synthesis2
- Iron-Catalyzed Indolizine Synthesis from Pyridines, Diazo Compounds, and Alkynes: Organic Letters Organic Letters. (nottingham.ac.uk)
- Au(I)-Catalyzed Synthesis of Trisubstituted Indolizines from 2-Propargyloxypyridines and Methyl Ketones. (isu.edu)
Ethyl1
- Home / Products / Caming Pharmaceutical Ltd / (S)-4-ETHYL-4-HYDROXY-7,8-DIHYDRO-1H-PYRANO[3,4-F]INDOLIZINE-3,6,10(4H)-TRIONE. (watsonnoke.com)
Heterocyclic2
- Indolizine is an heterocyclic compound with the formula C8H7N). (wikipedia.org)
- Treatment of 2,3-dihydro-2-methyl-3-phenyl-1 H -pyrazino[3,4,5- cd ]indolizine 2-oxides ( 5 ) with trifluoroacetic anhydride gave new heterocyclic six-membered betaines ( 6 ) which underwnet 1,3-dipolar cycloaddition reaction with dimethyl acetylenedicarboxylate and maleimides in hot toluene to yield the corresponding cycloadducts ( 7 ) and ( 8 ). (heterocycles.jp)
Derivatives2
- Conformational equilibria in novel C-nitroso derivatives of indolizines and 3- and 5-azaindolizines have been studied by NMR . (rsc.org)
- 1. Indazole and indolizine-3-carboxylic acid derivatives. (chemchart.com)
Synthesis of Indolizines2
- The iron (III) catalyzed synthesis of indolizines from commercially available alkyne, pyridine, and diazo precursors is reported. (nottingham.ac.uk)
- Amberlite-IRA-402 (OH) Ion Exchange Resin Mediated Synthesis of Indolizines, Pyrrolo. (csircentral.net)
Pyridines1
- Herein, we report an unprecedented recyclable stereoauxiliary aminocatalytic approach via aminosugars derived from biomass, which enable the efficient one-pot synthesis of desired trisubstituted indolizine-2-carbaldehydes via [3+2] annulations of acyl pyridines and α,ß-unsaturated aldehyde. (bvsalud.org)
Cyclization3
- Iodine-Mediated Domino Cyclization for One-Pot Synthesis of Indolizine-Fused Chromones via Metal-Free sp 3 C-H Functionalization. (nih.gov)
- Domino Knoevenagel condensation/intramolecular aldol cyclization route to diverse indolizines with densely functionalized pyridine units. (nih.gov)
- In 2014, Bi and co-workers reported the synthesis of pyrroles and indolizines from cyclization of 2-pyridyl alkynyl carbinols 16 with isocyanides (Scheme 11) [26]. (lempotee.fr)
Pyridine1
- A domino Michael-aldol double elimination route to indolizines having two different acyl groups at the C5 and C7 positions is described where chromone is employed as a two-carbon unit for the synthesis of a pyridine moiety for the first time. (nih.gov)
Precursors1
- Indolizine-carbaldehydes with the easily modifiable carbaldehyde group are important synthetic targets as versatile precursors for distinct indolizines. (bvsalud.org)
Methodologies2
- Thus, our approach advances the existing methodologies by providing a rich library of indolizine-2-aldehydes. (bvsalud.org)
- During his doctoral research, he discovered four different synthetic methodologies by which diversely functionalized indolizines can be constructed. (nih.gov)
Evaluation2
- 2. New indolizine-chalcones as potent inhibitors of human farnesyltransferase: Design, synthesis and biological evaluation. (nih.gov)
- Prior to joining NCATS in September 2022, Joshi earned his doctorate with a dissertation focused on the Expansion Of Indolizine Chemical Space: Synthesis of Poly-Functionalized Indolizines for Biological Evaluation. (nih.gov)
Compounds1
- This method can be used to synthesize a wide range of tertiary propargyl compounds such as pyrroles, indolizines, furans, and nitriles. (lempotee.fr)
Efficient3
- The article, "Indolizine-Based Scaffolds as Efficient and Versatile Tools: Application to the Synthesis of Biotin-Tagged Antiangiogenic Drugs," marks a milestone in the journal's growing prominence and popularity which ended 2017 with 1,008 published articles. (acs.org)
- However, the efficient one-pot construction of trisubstituted indolizine-2-carbaldehydes represents a long-standing challenge. (bvsalud.org)
- In addition, it delivers an efficient protocol for a set of late-stage diversification and targeted modifications of bioactive molecules or drugs, as showcased with 1,2,3-trisubstituted indolizine-2-carbaldehydes. (bvsalud.org)
Article1
- The 1,000th article describes the design and optimization of polyfunctional scaffolds based on a fluorescent indolizine core derivatized with various orthogonal groups. (acs.org)
Design1
- Molecular Design of Indolizine Derivative as Sensitizers for Organic Dye-Sensitized Solar Cells [J]. Acta Phys. (pku.edu.cn)