6770-41-8Relevant academic research and scientific papers
Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases
Brissonnet, Yoan,Assailly, Coralie,Saumonneau, Amélie,Bouckaert, Julie,Maillasson, Mike,Petitot, Clémence,Roubinet, Benoit,Didak, Blanka,Landemarre, Ludovic,Bridot, Clarisse,Blossey, Ralf,Deniaud, David,Yan, Xibo,Bernard, Julien,Tellier, Charles,Grandjean, Cyrille,Daligault, Franck,Gouin, Sébastien G.
, p. 2358 - 2365 (2019)
Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate-binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non-hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of V. cholerae, T. cruzi, and S. pneumoniae (NanA) sialidases. NanA was truncated from the catalytic and lectinic domains (NanA-L and NanA-C) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di- and polymeric thiosialosides. The NanA-L domain was shown to fully drive NanA binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce NanA and NanA-C catalytic activity with efficiency that was 3000-fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.
Synthesis and in vitro anti-influenza virus evaluation of novel sialic acid (C-5 and C-9)-pentacyclic triterpene derivatives
Han, Xu,Si, Long-Long,Shi, Yong-Ying,Fan, Zi-Bo,Wang, Shou-Xin,Tian, Zhen-Yu,Li, Man,Sun, Jia-Qi,Jiao, Ping-Xuan,Ran, Fu-Xiang,Zhang, Yong-Min,Zhou, De-Min,Xiao, Su-Long
, (2017/07/03)
The emergence of drug resistant variants of the influenza virus has led to a great need to identify novel and effective antiviral agents. In our previous study, a series of sialic acid (C-2 and C-4)-pentacyclic triterpene conjugates have been synthesized, and a five-fold more potent antiviral activity was observed when sialic acid was conjugated with pentacyclic triterpene via C-4 than C-2. It was here that we further reported the synthesis and anti-influenza activity of novel sialic acid (C-5 and C-9)-pentacyclic triterpene conjugates. Their structures were confirmed by ESI-HRMS,1H-NMR, and13C-NMR spectroscopic analyses. Two conjugates (26 and 42) showed strong cytotoxicity to MDCK cells in the CellTiter-Glo assay at a concentration of 100 μM. However, they showed no significant cytotoxicity to HL-60, Hela, and A549 cell lines in MTT assay under the concentration of 10 μM (except compound 42 showed weak cytotoxicity to HL-60 cell line (10 μM, ~53%)). Compounds 20, 28, 36, and 44 displayed weak potency to influenza A/WSN/33 (H1N1) virus (100 μM, ~20–30%), and no significant anti-influenza activity was found for the other conjugates. The data suggested that both the C-5 acetylamide and C-9 hydroxy of sialic acid were important for its binding with hemagglutinin during viral entry into host cells, while C-4 and C-2 hydroxy were not critical for the binding process and could be replaced with hydrophobic moieties. The research presented herein had significant implications for the design of novel antiviral inhibitors based on a sialic acid scaffold.
Neuramindase Inhibitor
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Page/Page column 11, (2008/12/05)
There are provided a novel compound having irreversible inhibitory activity against neuraminidase, a therapeutic agent and a detection agent for a disease involving neuraminidase. A compound represented by the following formula (I) and a salt thereof, a production method thereof, and an application method thereof, wherein: A1 represents an aryl group optionally having a substituent group or a heteroaryl group optionally having a substituent group;A2 represents —CX2R6 or —CHXR6 wherein X represents —F, —Cl, —Br, or —I;R1 represents a hydrogen atom or an alkyl group optionally having a substituent group;R2, R3, R4, and R5 represent each independently —OC(═O)R6, —OR6, —N(R6)2, —N3, —NHC(═NH)NHR6, —NHCOR6, —OSO3R6, —OPO3(R6)2, F, Cl, Br, or I; andR6 represents each independently a hydrogen atom, an alkyl group optionally having a substituent group, an aryl group optionally having a substituent group, or an optionally substituted heteroaryl group.
Syntheses of alkenylated carbohydrate derivatives toward the preparation of monolayers on silicon surfaces
De Smet, Louis C.P.M.,Pukin, Aliaksei V.,Stork, Gerrit A.,De Vos, C.H. Ric,Visser, Gerben M.,Zuilhof, Han,Sudh?lter, Ernst J.R.
, p. 2599 - 2605 (2007/10/03)
This note describes the synthesis of different alkenylated carbohydrate derivatives suitable for direct attachment to hydrogen-terminated silicon surfaces. The derivatives were alkenylated at the C-1 position, while the remaining hydroxyl groups were protected. The development of such new carbohydrate-based sensing elements opens the access to new classes of biosensors.
Structural Transformations of N-Acetylneuraminic Acid, XXV: Synthesis of Methyl-2-α-glycosides of 4-Epi-, 7-Epi-, 8-Epi-, and 7,8-Bis-epi-N-acetylneuraminic Acid
Bandgar, B. P.,Zbiral, E.
, p. 1075 - 1088 (2007/10/02)
The α-methylketoside of N-acetylneuraminic acid methylester (4) is transformed via the deacetylated compound 5 into the 9,8-O-isopropylidenderivative 6 which could be oxidized regioselectively by RuO4 to the corresponding 4-oxo-sialic acid analogue 7.Reduction with the borane-ammonia complex produces a 1:1 mixture of 6 and the desired α-methylketoside of 9,8-O-isopropyliden-4-epi-N-acetyl-neuraminic acid methylester (8).Removing of the isopropylidene group gives the α-methylketoside of 4-epi-N-acetylneuraminic acid methylester (9), which was further transformed to the ammonium salt of 4-epi-N-acetylneuraminic acid α-methylketoside (10).On the other hand compound 5 was turned into the 4,8,9-tri-O-t-butyldimethylsilylderivative 11a from which the corresponding 7-oxo-compound 12 by oxidation with RuO4 derives.The reduction of 12 with BH3-NH3 yielded a 1:1 mixtures of the starting material 11a and the desired 7-epi-derivative 13a which gives either via the purified peracetylated α-methylketoside of 7-epi-N-acetylneuraminic acid methylester (14) or a direct saponification the sodium salt of 7-epi-N-acetylneuraminic acid-α-methylketoside (15).Applying the Koenigs-Knorr procedure to the peracetylated 8-epi-N-acetylneuraminic acid methylester (16) gives rise to the formation of a 1:1 mixture of the corresponding α- and β-methylketosides 17 and 18 besides traces of the corresponding 2,3-dideoxy-2,3-didehydro-sialic acid derivative 19.After chromatographic separation of 17 further saponification leads to the sodium salt of 8-epi-N-acetylneuraminic acid-α-methylketoside (20).In an analogous procedure the sodium salt of 7,8-di-epi-N-acetylneuraminic acid-α-methylketoside (25) was prepared starting from the peracetylated 7,8-di-epi-N-acetylneuraminic acid methylester (21), whereby a mixture of the α- and β-methylketosides 22 and 23 was formed in a ratio 95:5 besides traces of the peracetylated 2,3-dideoxy-2,3-didehydro-sialic acid methylester (24).Keywords.Sialic acid analogoues; Methyl-α-ketosides of sialic aicd analogues.
Structural Variations of N-Acetylneuraminic Acid, 18 Synthesis of the Side Chain Stereo and Deoxy Analogs of 5-Acetamido-2,6-anhydro-3,5-dideoxy-D-erythro-L-manno-nonoic Acid
Bandgar, Babasaheb P.,Hartmann, Michael,Schmid, Walther,Zbiral, Erich
, p. 1185 - 1195 (2007/10/02)
The synthesis of 5-acetamido-2,6-anhydro-3,5-dideoxy-D-erythro-L-manno-nonoic acid (3b, 7,8-epi2-2-d-2-Heq-Neu5Ac) and sodium 5-acetamido-2,6-anhydro-3,5-dideoxy-L-threo-L-manno-nonoate (6b, 8-epi-2-d-2-Heq-Neu5Ac) could b
PHASE-TRANSFER-CATALYZED SYNTHESIS OF ARYL α-KETOSIDES OF N-ACETYLNEURAMINIC ACID. A 2-METHYLFLUORAN-6-YL GLYCOSIDE OF N-ACETYLNEURAMINIC ACID, 2-METHYL-6-(5-ACETAMIDO-3,5-DIDEOXY-α-D-glycero-D-galacto-NONULOPYRANOSYLONIC ACID)XANTHENE-9-SPIRO-1'-ISOBENZOFURAN-3'-ONE, A NEW SUBSTRATE..
Rothermel, Joerg,Faillard, Hans
, p. 29 - 40 (2007/10/02)
Glycosidation of N-acetylneuraminic acid by phase-transfer catalysis in chloroform-aqueous alkali gave several known and some new aryl α-ketosides in a short reaction time and in good yields.The 4-methylumbelliferyl α-ketoside, the standard substrate for neuraminidase, was prepared in a yield of up to 70percent.New Neu5Ac ketosides were prepared with fluorescein and the fluorescein analog, 2-methyl-6-hydroxyfluoran (2-methyl-6-hydroxyxanthene-9-spiro-1'-isobenzofuran-3'-one) as aglycons, the latter being synthesized from 2-(2-hydroxy-5-methylbenzoyl) benzoic acid and 3-fluorophenol.The α configuration was ascertained by 400-MHz 1H-NMR spectroscopy and by cleavage of the ketosides with neuraminidases from Vibrio cholerae and Clostridium perfringens.The enzymic hydrolysis of the 2-methylfluoran-6-yl ketoside gave Km values of 82 μM (V. cholerae) and 96 μM (C. perfringens).
