- Knockout of arabidopsis serotonin N-acetyltransferase-2 reduces melatonin levels and delays flowering
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Melatonin plays roles in both plant growth and defense. Serotonin N-acetyltransferase (SNAT) catalyzes formation of N-acetylserotonin (NAS) from serotonin. Plants contain two SNAT isogenes, which exhibit low-level amino acid homology. We studied the Arabidopsis thaliana SNAT2 (AtSNAT2) gene; we prepared recombinant SNAT2 protein and characterized a snat2 knockout mutant. The SNAT2 protein exhibited 27% amino acid homology with SNAT1; the Km was 232 μM and the Vmax was 2160 pmol/min/mg protein. Melatonin inhibited SNAT enzyme activity in vitro. SNAT2 mRNA was abundantly expressed in flowers; the melatonin content of flowers of the snat2 mutant was significantly less than that of wild-type flowers. The mutant exhibited delayed flowering and reductions in leaf area and biomass compared to the wild type. Delayed flowering was attributable to reductions in the expression levels of the gibberellin biosynthetic genes ent-kaurene synthase (KS) and FLOWERING LOCUS T (FT).
- Lee, Hyoung Yool,Lee, Kyungjin,Back, Kyoungwhan
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Read Online
- Synthesis and evaluation of the antiovulatory activity of a variety of melatonin analogues
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A series of melatonin analogues was synthesized and examined for ovulation-blocking activity. Deviation from the 5-methoxy group or substitution of the 1 position prevented activity. Activity was not particularly sensitive to minor variations in the N-acyl group nor was it significantly altered by methylation of position 2 or the α-methylene; however, a pronounced enhancement resulted from halogenation of the 6 position.
- Flaugh,Crowell,Clemens,Sawyer
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Read Online
- Mutasynthesis of Physostigmines in Myxococcus xanthus
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The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by applying a simple feeding strategy include the promising drug candidate phenserine, which was previously accessible only by total synthesis.
- Winand, Lea,Schneider, Pascal,Kruth, Sebastian,Greven, Nico-Joel,Hiller, Wolf,Kaiser, Marcel,Pietruszka, J?rg,Nett, Markus
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Read Online
- Synthesis process of melatonin intermediate N-acetyl serotonin
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The invention relates to the technical field of biological semi-synthesis, and provides a synthesis process of a melatonin intermediate N-acetyl serotonin, wherein the synthesis process comprises the following steps: S1, adding serotonin hydrochloride into dichloromethane, and stirring; S2, adding triethylamine and sodium bicarbonate, stirring into a suspension, and cooling in the process; S3, adding an acetylation reagent; S4, heating and stirring the reaction mixture; and S5, after the reaction is finished, carrying out post-treatment. According to the technical scheme, the problems that in the prior art, the technological process is complex, and the product quality is poor are solved.
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Paragraph 0026-0041
(2021/09/15)
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- BIOMARKER PANEL TARGETED TO DISEASES DUE TO MULTIFACTORIAL ONTOLOGY OF GLYCOCALYX DISRUPTION
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The present disclosure provides biomarkers useful as companion diagnostics for detecting glycocalyx-based disease that is amenable to treatment using compounds designed for improving the condition of the glycocalyx and/or reducing inflammation and/or oxidative damage, as well as related compositions, kits, and methods.
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- Biocatalytic C3-Indole Methylation—A Useful Tool for the Natural-Product-Inspired Stereoselective Synthesis of Pyrroloindoles
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Enantioselective synthesis of bioactive compounds bearing a pyrroloindole framework is often laborious. In contrast, there are several S-adenosyl methionine (SAM)-dependent methyl transferases known for stereo- and regioselective methylation at the C3 position of various indoles, directly leading to the formation of the desired pyrroloindole moiety. Herein, the SAM-dependent methyl transferase PsmD from Streptomyces griseofuscus, a key enzyme in the biosynthesis of physostigmine, is characterized in detail. The biochemical properties of PsmD and its substrate scope were demonstrated. Preparative scale enzymatic methylation including SAM regeneration was achieved for three selected substrates after a design-of-experiment optimization.
- Schneider, Pascal,Hen?en, Birgit,Paschold, Beatrix,Chapple, Benjamin P.,Schatton, Marcel,Seebeck, Florian P.,Classen, Thomas,Pietruszka, J?rg
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p. 23412 - 23418
(2021/09/20)
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- Characterization of arylalkylamine n-acyltransferase from tribolium castaneum: an investigation into a potential next-generation insecticide target
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The growing issue of insecticide resistance has meant the identification of novel insecticide targets has never been more important. Arylalkylamine N-acyltransferases (AANATs) have been suggested as a potential new target. These promiscuous enzymes are involved in the N-acylation of biogenic amines to form N-acylamides. In insects, this process is a key step in melanism, hardening of the cuticle, removal of biogenic amines, and in the biosynthesis of fatty acid amides. The unique nature of each AANAT isoform characterized indicates each organism accommodates an assembly of discrete AANATs relatively exclusive to that organism. This implies a high potential for selectivity in insecticide design, while also maintaining polypharmacology. Presented here is a thorough kinetic and structural analysis of AANAT found in one of the most common secondary pests of all plant commodities in the world, Tribolium castaneum. The enzyme, named TcAANAT0, catalyzes the formation of short-chain N-acylarylalkylamines, with short-chain acyl-CoAs (C2-C10), benzoyl-CoA, and succinyl-CoA functioning in the role of acyl donor. Recombinant TcAANAT0 was expressed and purified from E. coli and was used to investigate the kinetic and chemical mechanism of catalysis. The kinetic mechanism is an ordered sequential mechanism with the acyl-CoA binding first. pH-rate profiles and site-directed mutagenesis studies identified amino acids critical to catalysis, providing insights about the chemical mechanism of TcAANAT0. A crystal structure was obtained for TcAANAT0 bound to acetyl-CoA, revealing valuable information about its active site. This combination of kinetic analysis and crystallography alongside mutagenesis and sequence analysis shines light on some approaches possible for targeting TcAANAT0 and other AANATs for novel insecticide design.
- Anderson, Ryan L.,Chen, Yu,Gelis, Ioannis,Leahy, James W.,Lewandowski, Eric M.,Mccaskey, Angelica N.,Merkler, David J.,O'flynn, Brian G.,Prins, Karin Claire,Rios-Guzman, Nasha M.,Shepherd, Britney A.,Suarez, Gabriela
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p. 513 - 523
(2020/03/11)
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- Flow-based enzymatic synthesis of melatonin and other high value tryptamine derivatives: A five-minute intensified process
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To increase the uptake of biocatalytic processes by industry, it is essential to demonstrate the reliability of enzyme-based methodologies directly applied to the production of high value products. Here, a unique, efficient, and sustainable enzymatic platform for the multi-gram synthesis of melatonin, projected to generate around 1.5 billion U.S. dollars worldwide by 2021, and its analogues was developed. The system exploits the covalent immobilization of MsAcT (transferase from Mycobacterium smegmatis) onto agarose beads increasing the robustness and longevity of the immobilized biocatalyst. The fully-automated process deriving from the integration between biocatalysis and flow chemistry is designed to maximize the overall yields (58-92%) and reduce reaction times (5 min), overcoming the limitation often associated with bioprocesses and bridging the gap between lab scale and industrial production.
- Contente, Martina Letizia,Farris, Stefano,Tamborini, Lucia,Molinari, Francesco,Paradisi, Francesca
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supporting information
p. 3263 - 3266
(2019/06/24)
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- Comprehensive kinetic and substrate specificity analysis of an arylsulfatase from Helix pomatia using mass spectrometry
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Sulfatases hydrolyze sulfated metabolites to their corresponding alcohols and are present in all domains of life. These enzymes have found major application in metabolic investigation of drugs, doping control analysis and recently in metabolomics. Interest in sulfatases has increased due to a link between metabolic processes involving sulfated metabolites and pathophysiological conditions in humans. Herein, we present the first comprehensive substrate specificity and kinetic analysis of the most commonly used arylsulfatase extracted from the snail Helix pomatia. In the past, this enzyme has been used in the form of a crude mixture of enzymes, however, recently we have purified this sulfatase for a new application in metabolomics-driven discovery of sulfated metabolites. To evaluate the substrate specificity of this promiscuous sulfatase, we have synthesized a series of new sulfated metabolites of diverse structure and employed a mass spectrometric assay for kinetic substrate hydrolysis evaluation. Our analysis of the purified enzyme revealed that the sulfatase has a strong preference for metabolites with a bi- or tricyclic aromatic scaffold and to a lesser extent for monocyclic aromatic phenols. This metabolite library and mass spectrometric method can be applied for the characterization of other sulfatases from humans and gut microbiota to investigate their involvement in disease development.
- Correia, Mário S.P.,Ballet, Caroline,Meistermann, Hannes,Conway, Louis P.,Globisch, Daniel
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p. 955 - 962
(2019/02/09)
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- New enzymatic and mass spectrometric methodology for the selective investigation of gut microbiota-derived metabolites
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Gut microbiota significantly impact human physiology through metabolic interaction. Selective investigation of the co-metabolism of bacteria and their human host is a challenging task and methods for their analysis are limited. One class of metabolites associated with this co-metabolism are O-sulfated compounds. Herein, we describe the development of a new enzymatic assay for the selective mass spectrometric investigation of this phase II modification class. Analysis of human urine and fecal samples resulted in the detection of 206 sulfated metabolites, which is three times more than reported in the Human Metabolome Database. We confirmed the chemical structure of 36 sulfated metabolites including unknown and commonly reported microbiota-derived sulfated metabolites using synthesized internal standards and mass spectrometric fragmentation experiments. Our findings demonstrate that enzymatic sample pre-treatment combined with state-of-the-art metabolomics analysis represents a new and efficient strategy for the discovery of unknown microbiota-derived metabolites in human samples. Our described approach can be adapted for the targeted investigation of other metabolite classes as well as the discovery of biomarkers for diseases affected by microbiota.
- Ballet, Caroline,Correia, Mário S. P.,Conway, Louis P.,Locher, Theresa L.,Lehmann, Laura C.,Garg, Neeraj,Vujasinovic, Miroslav,Deindl, Sebastian,L?hr, J.-Matthias,Globisch, Daniel
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p. 6233 - 6239
(2018/08/07)
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- COMPOUNDS DERIVED FROM 3-ALKYLAMINO-1H-INDOLE ACRYLATE, AND THE USE THEREOF IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
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The invention relates to the methods for producing derivatives of 3-alkylamino-1H-indole acrylate (I) with transcription factor Nrf2-inducing activity, free radical scavenging activity and neuroprotective ability. The invention also relates to the use of the derivatives according to the invention for the treatment of diseases, the pathogenesis of which involves oxidative stress, or diseases involving the deregulation of the activity of phase II genes activated by the factor Nrf2, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, ictus or amyotrophic lateral sclerosis.
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Paragraph 0066
(2017/09/04)
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- Mechanistic and structural analysis of Drosophila melanogaster arylalkylamine N-acetyltransferases
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(Chemical Equation Presented). Arylalkylamine N-acetyltransferase (AANAT) catalyzes the penultimate step in the biosynthesis of melatonin and other N-acetylarylalkylamides from the corresponding arylalkylamine and acetyl-CoA. The N-acetylation of arylalkylamines is a critical step in Drosophila melanogaster for the inactivation of the bioactive amines and the sclerotization of the cuticle. Two AANAT variants (AANATA and AANATB) have been identified in D. melanogaster , in which AANATA differs from AANATB by the truncation of 35 amino acids from the N-terminus. We have expressed and purified both D. melanogaster AANAT variants (AANATA and AANATB) in Escherichia coli and used the purified enzymes to demonstrate that this N-terminal truncation does not affect the activity of the enzyme. Subsequent characterization of the kinetic and chemical mechanism of AANATA identified an ordered sequential mechanism, with acetyl-CoA binding first, followed by tyramine. We used a combination of pH-activity profiling and site-directed mutagenesis to study prospective residues believed to function in AANATA catalysis. These data led to an assignment of Glu-47 as the general base in catalysis with an apparent pKa of 7.0. Using the data generated for the kinetic mechanism, structure-function relationships, pH-rate profiles, and site-directed mutagenesis, we propose a chemical mechanism for AANATA.
- Dempsey, Daniel R.,Jeffries, Kristen A.,Bond, Jason D.,Carpenter, Anne-Marie,Rodriguez-Ospina, Santiago,Breydo, Leonid,Caswell, K. Kenneth,Merkler, David J.
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p. 7777 - 7793
(2015/02/19)
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- TRYPTAMINE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN GASTROPATHY
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The synthesis and evaluation of gastroprotective effect of different tryptamine derivatives. Tryptamine derivatives have been synthesized by formation of amide or ester with some known anti oxidant molecules. These derivatives show excellent antioxidant property in vitro. Among all the derivatives the compound SEGA (3a), that was prepared by the combination of serotonin with gallic acid shows the greater antioxidant property than the other synthesized compounds both in vivo and in vitro. SEGA(3a) shows the gastroprotective effect against NSAIDs (indomethacin or diclofenac)-induced gastropathy in dose dependent manner and also accelerates the healing from injury. It prevents the NSAIDs-induced mitochondrial oxidative stress in vivo. This derivative prevents NSAID-induced mitochondrial oxidative stress-mediated apoptosis in vivo by preventing the activation of caspase 9 and caspase-3 and restores NSAIDs-mediated collapse of mitochondroial transmembrane potential and dehydrogenase activity. SEGA (3a) plays an important role as an iron chelator as well as intra mitochondrial ROS scavenger. Thus, SEGA (3a) is a potent antioxidant antiapototic molecule, which efficiently prevents NSAID-induced gastropathy and stress or alcohol-mediated gastric damage.
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Paragraph 0137; 0138
(2013/08/14)
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- TRYPTAMINE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN GASTROPATHY
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The present invention concerns the synthesis and evaluation of gastroprotective effect of different tryptamine derivatives. Tryptamine derivatives have been synthesized by formation of amide or ester with some known anti oxidant molecules. These derivatives show excellent antioxidant property in vitro. Among all the derivatives the compound SEGA (3 a), that was prepared by the combination of serotonin with gallic acid shows the greater antioxidant property than the other synthesized compounds both in vivo and in vitro. SEGA(3a) shows the gastroprotective effect against NSAIDs (indomethacin or diclofenac)-induced gastropathy in dose dependent manner and also accelerates the healing from injury. It prevents the NSAIDs-induced mitochondrial oxidative stress in vivo. This derivative prevents NSAID-induced mitochondrial oxidative stress-mediated apoptosis in vivo by preventing the activation of caspase 9 and caspase-3 and restores NSAIDs-mediated collapse of mitochondroial transmembrane potential and dehydrogenase activity. SEGA (3 a) plays an important role as an iron chelator as well as intra mitochondrial ROS scavenger. Thus, SEGA (3 a) is a potent antioxidant antiapototic molecule, which efficiently prevents NSAID-induced gastropathy and stress or alcohol -mediated gastric damage.
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Page/Page column 11; 28-29
(2012/04/04)
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- SEPIAPTERIN REDUCTASE INHIBITORS FOR THE TREATMENT OF PAIN
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Disclosed herein are small molecule heterocyclic inhibitors of sepiapterin reductase (SPR), and pro-drugs and pharmaceutically acceptable salts thereof. The Also featured are pharmaceutical compositions of the compounds and uses of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, and neuropathic pain)
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Page/Page column 39
(2011/05/05)
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- N-acetyl-5-arylalkoxytryptamine analogs: Probing the melatonin receptors for MT1-selectivity
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A series of melatonin analogs obtained by the replacement of the ether methyl group with larger arylalkyl and aryloxyalkyl substituents was prepared in order to probe the melatonin receptors for MT1-selectivity. The most MT1-selective agents 11 and 15 were substituted with a Ph(CH 2)3 or a PhO(CH2)3 group. Compounds 11 and 15 displayed 11.5-fold and 11-fold higher affinity for the MT1 receptors than for the MT2 subtype. Interestingly, in our binding assay 11 and 15 have shown considerably higher MT1-affinity and selectivity than the reference ligand, the dimeric agomelatine 1a. The synthesis and pharmacological evaluation of a novel series of MLT analogs obtained by replacing the ether methyl group with arylalkyl and aryloxyalkyl moieties is described here. The results indicate for compounds 11 and 15 considerably higher MT1-affinity and selectivity than the reference ligand, the dimeric agomelatine 1a. Copyright
- Markl, Christian,Clafshenkel, William P.,Attia, Mohamed I.,Sethi, Shalini,Witt-Enderby, Paula A.,Zlotos, Darius P.
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experimental part
p. 666 - 674
(2012/06/17)
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- Molecular evolution of multiple arylalkylamine N-acetyltransferase (AANAT) in fish
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Arylalkylamine N-acetyltransferase (AANAT) catalyzes the transfer of an acetyl group from acetyl coenzyme A (AcCoA) to arylalkylamines, including indolethylamines and phenylethylamines. Multiple aanats are present in teleost fish as a result of whole genome and gene duplications. Fish aanat1a and aanat2 paralogs display different patterns of tissue expression and encode proteins with different substrate preference: AANAT1a is expressed in the retina, and acetylates both indolethylamines and phenylethylamines; while AANAT2 is expressed in the pineal gland, and preferentially acetylates indolethylamines. The two enzymes are therefore thought to serve different roles. Here, the molecular changes that led to their specialization were studied by investigating the structure-function relationships of AANATs in the gilthead seabream (sb, Sperus aurata). Acetylation activity of reciprocal mutated enzymes pointed to specific residues that contribute to substrate specificity of the enzymes. Inhibition tests followed by complementary analyses of the predicted three-dimensional models of the enzymes, suggested that both phenylethylamines and indolethylamines bind to the catalytic pocket of both enzymes. These results suggest that substrate selectivity of AANAT1a and AANAT2 is determined by the positioning of the substrate within the catalytic pocket, and its accessibility to catalysis. This illustrates the evolutionary process by which enzymes encoded by duplicated genes acquire different activities and play different biological roles.
- Zilberman-Peled, Bina,Bransburg-Zabary, Sharron,Klein, David C.,Gothilf, Yoav
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experimental part
p. 906 - 921
(2011/06/27)
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- Substituted biphenyl derivatives, method for preparing same and pharmaceutical compositions containing same
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The invention relates to compound of formula (I): wherein: B represents hydrogen, COOR, CONRR′, or (C1-C6)alkyl substituted by COOR, CONRR′, or OR, G1 represents —X′—(CH2)n—X—(CH2)m—X″—chain wherein X, X′, X″, n and m are as defined in the description, Cy represents a grouping of formula (II) or (III): G2 represents alkylene chain as defined in the description, and A represents NRCOR′, NRCSR′, CONRR′, CSNRR′, NRCONR′R″, or NRCSNR′R″, and medicinal products containing the same which are useful in treating or preventing melatoninergic disorders.
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- Covalent conjugates of biologically-active compounds with amino acids and amino acid derivatives for targeting to physiologically-protected sites
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This invention herein describes a method of facilitating the entry of drugs into cells and tissues at physiologically protected sites at pharmacokinetically useful levels and also a method of targeting drugs to physiologically protected sites in vivo. Also provided are drug conjugates with an amino acid or derivative thereof for facilitating such targeted drug delivery. The conjugates and methods of this invention provide an advance over other drug targeting methods known in the prior art, because the invention provides drug concentrations in such physiologically protected sites that can reach therapeutically-effective levels after administration of systemic levels much lower than are currently administered to achieve a therapeutic dose. This technology is appropriate for use with psychotropic, neurotropic, neurological, antibiotic, antibacterial, antimycotic, antiviral, antiproliferative or antineoplastic drugs, agents and conjugates, for rapid and efficient introduction of such agents across, e.g., the blood-brain barrier. Further, the invention provides means for retention and prolonged enzymatic release of such drugs, agents and conjugates comprising the conjugates of the invention, in the brain and central nervous system and other physiologically-protected sites.
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- Tryptamine analogs with 5-HT1D selectivity
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Described herein are tryptamine analogs that display high binding affinity and selectivity for the 5-HT1Dβ receptor, of the formula: STR1 wherein R 1 represents a chain selected from C 8-11 alkyl, C 7-10 alkoxy, C 8-11 alkanoyl and C 7-10 alkanoyloxy wherein said chain is optionally substituted by hydroxyl, C 1-4 alkyl or C 1-4 alkoxy and wherein one of the intervening carbons of said chain is optionally replaced with a heteroatom selected from oxygen, nitrogen and sulfur;R 2 and R 3 each independently represent H or C 1-3 alkyl; andR 4 represents H, C 1-4 alkyl, aryl or arylC 1-4 alkyl;The compounds are useful as reagents for receptor identification and in receptor-based drug screening programs, and can also be used therapeutically to treat conditions for which administration of a 5-HT1D ligand is indicated, for example in the treatment of migraine.
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- Binding of O-alkyl derivatives of serotonin at human 5-HT1Dβ receptors
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In humans, 5-HT1D serotonin receptors represent terminal autoreceptors, and there is some evidence that 5-HT1D ligands may be useful in the treatment of migraine. The most widely used 5-HT1D agonist is sumatriptan; however, this agent reportedly displays little selectivity for 5-HT1D versus 5-HT1A receptors. To identify novel serotonergic agents with enhanced 5-HT1D versus 5-HT1A selectivity, we attempted to take advantage of possible differences in the regions of bulk tolerance associated with the 5-position of the 5-HT binding sites for these two populations of receptors. Examination of a series of 5-(alkyloxy)tryptamine derivatives demonstrated that compounds with unbranched alkyl groups of up to eight carbon atoms bind with high affinity at human 5-HT1Dβ receptors (K(i) 300-fold). Branching of the alkyl chain, to 5-[(7,7-dimethylheptyl)oxy]tryptamine (15), results in an agent with somewhat lower affinity (5-HT1Dβ K(i) = 2.3 nM) but with greater (i.e., 400-fold) 5-HT1D versus 5-HT1A selectivity. Replacement of the oxygen atom of 10 with a methylene group (i.e., 20), replacement of the O-proximate methylene with a carbonyl group (i.e., ester 26), or cyclization of the aminoethyl moiety to a carbazole (e.g., 34, 36) or β- carboline (i.e., 37), result in reduced affinity and/or selectivity. None of the compounds examined displayed significant selectivity for 5-HT1Dβ versus 5-HT1Dα sites; nevertheless, compounds 10 (recently shown to behave as a 5- HT1D agonist) and 15 represent the most 5-HT1D versus 5-HT1A selective agents reported to date.
- Glennon, Richard A.,Hong, Seoung-Soo,Bondarev, Mikhail,Law, Ho,Dukat, Malgorzata,Rakhit, Suman,Power, Patricia,Fan, Ermei,Kinneau, Diana,Kamboj, Rajender,Teitler, Milt,Herrick-Davis, Katharine,Smith, Carol
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p. 314 - 322
(2007/10/03)
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- Structure-activity relationships for substrates and inhibitors of pineal 5-hydroxytryptamine-N-acetyltransferase: Preliminary studies
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Tryptamine, (1-naphthyl)ethylamine and phenethylamine derivatives were tested as substrates of ovine pineal serotonin-N-acetyl transferase (5-HT-NAT), a key enzyme involved in the synthesis of melatonin. Almost all of the indole derivatives possessed affinity similar to that of tryptamine (K(m) - 0.05 mM), while the substituted naphthalene and phenyl derivatives were less potent. However, the K, values seem be influenced by the steric hindrance and polar properties of the substituent. V(max) values for the naphthyl and phenyl derivatives were generally 10-20-fold higher than those of the indole derivatives and no clear structure-activity relationship was observed. Melatonin and several bioisoteric derivatives were shown to be inhibitors of 5-HT-N-acetyltransferase. Preliminary data suggested that over the 5-50-μM concentration range, melatonin was a competitive inhibitor (IC50 = 10 μM) with a concentration-dependent inhibitory effect on its own synthesis in the pineal gland. However, the bioisosteric naphthalene derivatives were characterized instead as mixed inhibitors. (1-Napthyl)ethylacetamido, a putative melatoninergic antagonist, was also shown to be an inhibitor of 5-HT-N-acetyltransferase (IC50 = 8 μM) and is a promising tool for the regulation of melatonin synthesis and the understanding of its role.
- Shen, Shuren,Bremont, Beatrice,Serraz, Isabelle,Andrieux, Jean,Poncet, Annie,Mathe-Allainmat, Monique,Chanut, Evelyne,Trouvin, Jean-Hugues,Langlois, Michel
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p. 133 - 140
(2007/10/03)
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- A novel dimerization of 1-hydroxyindoles
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1-Hydroxyindoles are sensitive to acids and undergo four types of competing reactions; dehydroxylation, nucleophilic substitution, dimerization, and formation of hexacyclic dimer. The direction of the reaction seems to be determined depending on the subtle balance of substrate structures, acids, and reaction conditions. Stuctures of variety of products are unequivocally determined by X-ray single crystallographic analyses and chemical correlations.
- Hasegawa, Masakazu,Tabata, Mutsuko,Satoh, Keiichi,Yamada, Fumio,Somei, Masanori
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p. 2333 - 2342
(2007/10/03)
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- Nucleophilic Substitution Reaction Of 1-Hydroxytryptophan And 1-Hydroxytryptamine Derivatives (Regioselective Syntheses Of 5-Substituted Derivatives Of Tryptophan And Tryptamine)
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Regioselective nucleophilic substitution at the 5-position of indole nucleus was observed in the reaction of 1-hydroxytryptophan and 1-hydroxytryptamine derivatives with acids, suggesting the mechanism of serotonin formation in the central nervous system.
- Somei, Masanori,Fukui, Yoshikazu
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p. 1859 - 1866
(2007/10/02)
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- Preparation of serotonine and derivatives
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A process for the separation of serotonine from coffee wax wherein a solution of coffee wax is subjected to alkaline hydrolysis using a strong base in the presence of water in an inert atmosphere after which the reaction medium containing the serotonine is recovered characterized in that the solvent for the coffee wax is a compound having the general formula II: wherein R is hydrogen or an alkyl group containing from 1 to 4 carbon atoms, x is 0 or 1 and n is an integer from 2 to 4 with the proviso that x cannot be 1 when n is 3 or 4. N-acetyl serotonine is prepared by acetylating serotonine to N, O-diacetyl serotonine and then selectively hydrolyzing the O-acetyl group. Melatonine is obtained by methylating N-acetyl serotonine in the 5-position. Mexamine is obtained by de-acetylating melatonine in a hot alkaline solution containing a water-insoluble alcohol and acidifying the alcohol phase with hydrochloric acid.
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