- Assembly and inhibitory activity of monovalent mannosides terminated with aromatic methyl esters: The effect of naphthyl groups
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A series of monovalent α-D-mannoside ligands terminated with aromatic methyl esters have been synthesized in excellent yields using the Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition (“click chemistry”). These mannosides were designed to have a unique aglycone moiety (tail) that combines a triazole ring attached to aromatic methyl esters via a six carbon alkyl chain. The mannose unit of these ligands was linked at the ortho, meta, and para positions of substituted methyl benzoates and 1-, 3-, and 6-substituted methyl 2-napthaoates. In hemagglutination assays, ligands (32A-38A) showed better inhibitory activities than the standard inhibitor, methyl α-D-mannopyranoside. Overall, the naphthyl-based mannoside ligand (37A) showed the best activity and therefore merits further development.
- Al-Mughaid, Hussein,Al-Zoubi, Raed M.,Khazaaleh, Maha,Grindley, T. Bruce
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- Penicacids A-C, three new mycophenolic acid derivatives and immunosuppressive activities from the marine-derived fungus Penicillium sp. SOF07
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Three new mycophenolic acid derivatives, penicacids A-C (1-3), together with two known analogues, mycophenolic acid (MPA, 4) and 4′-hydroxy-MPA (5), were isolated from a fungus Penicillium sp. SOF07 derived from a South China Sea marine sediment. The structures of compounds 1-3 were elucidated on the basis of MS and NMR (1H, 13C, HSQC and HMBC) data analyses and comparisons with the known compounds. Structure-activity relationship studies of compounds 1-5 focused on inosine-monophosphate dehydrogenase inhibition revealed that hydroxylation at C-4′, methylation at C-7-OH, dual hydroxylation at C-2′/C-3′ double bond of MPA diminished bioactivity whereas glucosyl hydroxylation at C-4′ correlated to bioactivity comparable to that observed for MPA.
- Chen, Ziming,Zheng, Zhihui,Huang, Hongbo,Song, Yongxiang,Zhang, Xuelian,Ma, Junying,Wang, Bo,Zhang, Changsheng,Ju, Jianhua
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- Improved synthesis of per-O-acetylated C1 hydroxyglycopyranose and structural study as non-covalent organic framework
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An improved method for the synthesis of per-O-acetylated C-1-hydroxyglycopyranose was developed by hydrolysis of per-O-acetylated glycopyranosyl α-chlorides derived from sugars with C-2 axial acetates for example l-rhamnose and d-mannose. 2,3,4-Tri-O-acetyl-α-l-rhamnopyranose crystallized in tetragonal space group I4, a rare phenomenon in carbohydrate literature. The three dimensional packing of the molecule with the help of regular hydrogen bond and C-H···O interactions resulted in the formation of porous framework showing channels with pore size 7 A?.
- Singhamahapatra, Anadi,Sahoo, Laxminarayan,Paul, Katuri J.V.,Varghese, Babu,Loganathan, Duraikkannu
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- Synthesis of carbohydrate-grafted glycopolymers using a catalyst-free, perfluoroarylazide-mediated fast staudinger reaction
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Glycopolymers have gained increasing importance in investigating glycan-lectin interactions, as drug delivery vehicles and in modulating interactions with proteins. The synthesis of these glycopolymers is still a challenging and rigorous exercise. In this
- Ndugire, William,Wu, Bin,Yan, Mingdi
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- Folding control of a non-natural glycopeptide using saccharide-coded structural information for polypeptides
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We synthesized "glyco-arylopeptides", whose folding structure significantly changes depending on the kind of saccharide in their side chain. The saccharide moiety interacts with the main chain via hydrogen bonding, and the non-natural polypeptides form two well-defined architectures - (P)-31- and (M)-41-helices - depending on the length of the saccharide chains and even the configuration of a single stereo-genic center in the epimers.
- Fujii, Naoka,Haino, Takeharu,Ishido, Yuki,Kanbayashi, Naoya,Okamura, Taka-Aki,Onitsuka, Kiyotaka
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- Sialidase substrate specificity studies using chemoenzymatically synthesized sialosides containing C5-modified sialic acids
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para-Nitrophenol-tagged sialyl galactosides containing sialic acid derivatives in which the C5 hydroxyl group of sialic acids was systematically substituted with a hydrogen, a fluorine, a methoxyl or an azido group were successfully synthesized using an efficient chemoenzymatic approach. These compounds were used as valuable probes in high-throughput screening assays to study the importance of the C5 hydroxyl group of sialic acid in the recognition and the cleavage of sialoside substrates by bacterial sialidases.
- Cao, Hongzhi,Li, Yanhong,Lau, Kam,Muthana, Saddam,Yu, Hai,Cheng, Jiansong,Chokhawala, Harshal A.,Sugiarto, Go,Zhang, Lei,Chen, Xi
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- THE SELECTIVE BOND CLEAVAGE OF ALDOHEXOSES BY THE IRON(III) CHLORIDE-CATALYZED PHOTOREACTION
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Photoreaction of D-glucose, D-mannose, and D-galactose in pyridine in the presence of iron(III) chloride induced a selective bond cleavage at C1-C2 position, and produced corresponding 4-O-formyl-D-aldopentopyranoses.
- Ichikawa, Shuji,Sato, Tadashi
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- Efficient assembly of oligomannosides using the hydrophobically assisted switching phase method
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The hydrophobically assisted switching phase (HASP) method was applied in the assembly of oligomannosides. A new mannosyl donor with high reactivity was selected after a series of optimization studies, which was suitable for the synthesis of oligomannosides via the HASP method. The practicability of the HASP method towards the synthesis of branched oligosaccharides was explored and two branched penta-mannosides were assembled efficiently.
- Meng, Shuai,Tian, Tian,Han, Dong,Wang, Lin-Na,Tang, Shao-Geng,Meng, Xiang-Bao,Li, Zhong-Jun
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- Click chemistry approach for the synthesis of water-soluble glycodendrimer with triazole as building unit
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A new family of chiral glycodendrimers scaffolds containing di-, tetra- and octavalent glucose residues as peripheral unit and with 1,2,3-triazole as building unit has been synthesized through Cu(I)-catalyzed click chemistry by convergent approach. Georg
- Rajakumar, Perumal,Anandhan, Ramasamy,Kalpana, Venkatesan
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- Task-oriented use of ionic liquids: Efficient acetylation of alcohols and phenols
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The ionic liquid 1-butyl-3-methylimidazolium acetate proves to be an excellent reaction medium for the acetylation of alcohols and phenols, providing better conditions than the acidic 1-butyl-3-methylimidazolium bisulfate. Reactions were carried at room temperature, with only a 10% excess of acylating agent and with no other solvent or catalyst added.
- López, Ignacio,Bravo, José Luis,Caraballo, Manuel,Barneto, José Luis,Silvero, Guadalupe
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- Surface-engineered dendrimeric nanoconjugates for macrophage-targeted delivery of amphotericin B: Formulation development and in vitro and in vivo evaluation
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The present study aimed to develop an optimized dendrimeric delivery system for amphotericin B (AmB). Fifth-generation (5.0G) poly(propylene imine) (PPI) dendrimers were synthesized, conjugated with mannose, and characterized by use of various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H-NMR) spectroscopic analysis, and atomic force microscopy (AFM). Mannose-conjugated 5.0G PPI (MPPI) dendrimers were loaded with AmB and evaluated for drug loading efficiency, in vitro drug release profile, stability, hemolytic toxicity to human erythrocytes, cytotoxicity to and cell uptake by J774A.1 macrophage cells, antiparasitic activity against intracellular Leishmania donovani amastigotes, in vivo pharmacokinetic and biodistribution profiles, drug localization index, toxicity, and antileishmanial activity. AFM showed the nanometric size of the MPPI dendrimers, with a nearly globular architecture. The conjugate showed a good entrapment efficiency for AmB, along with pH-sensitive drug release. Highly significant reductions in toxicity toward human erythrocytes and macrophage cells, without compromising the antiparasitic activity of AmB, were observed. The dendrimeric formulation of AmB showed a significant enhancement of the parasiticidal activity of AmB toward intramacrophagic L. donovani amastigotes. In the in vitro cell uptake studies, the formulation showed selectivity toward macrophages, with significant intracellular uptake. Further pharmacokinetic and organ distribution studies elucidated the controlled delivery behavior of the formulation. The drug localization index was found to increase significantly in macrophage-rich organs. In vivo studies showed a biocompatible behavior of MPPIA, with negligible toxicity even at higher doses, and promising antileishmanial activity. From the results, we concluded that surface-engineered dendrimers may serve as optimized delivery vehicles for AmB with enhanced activity and low or negligible toxicity.
- Jain, Keerti,Verma, Ashwni Kumar,Mishra, Prabhat Ranjan,Jain, Narendra Kumar
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- Surface functionalization of nanomaterials with dendritic groups: Toward enhanced binding to biological targets
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A diverse array of nanomaterials ranging from polymer assemblies to nanoparticles has been under development for biomedical applications in recent years. A key aspect of these applications is the ability to target the materials to the desired locations in vivo by exploiting their size or through the conjugation of active targeting groups. While nanoscale scaffolds may provide advantages such as the multivalent presentation of targeting ligands, the binding of these ligands may also be inhibited by interfering polymer chains at their surfaces. This aspect was investigated here by preparing poly(butadiene-block-ethylene oxide) vesicles and dextran-coated iron oxide nanoparticles functionalized with dendritic and nondendritic displays of mannose, a well-known multivalent ligand. The binding of these systems to the mannose-binding protein Concanavalin A was compared using a hemagglutination assay. It was found that the dendritic systems exhibited 1-2 orders of magnitude enhancement in binding affinity relative to the nondendritic displays. This result is attributed to the ability of the dendritic groups to overcome steric inhibition by polymer chains at the material surface and also to the presentation of ligands in localized clusters. It is anticipated that these results should be applicable to a wide range of nanomaterials with polymers at their surfaces and that the method by which biological ligands are conjugated to the surfaces of nanoparticles and polymer assemblies should be carefully considered.
- Martin, Amanda L.,Li, Bo,Gillies, Elizabeth R.
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- Structure and stereochemistry of a novel bioactive sphingolipid from a Calyx sp.
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Bioassay-directed fractionation of a sponge of the genus Calyx using a yeast bioassay for DNA-damaging agents yielded the novel sphingolipid calyxoside (1) as the major bioactive constituent. The structure of 1 was assigned as 1,3,26-trihydroxy-2,27-diaminooctacosan-18-one-1-β-D-glucoside by 1H- and 13C NMR, DEPT, DQCOSY, HMQC, and HMBC spectra. The carbonyl group was located at C-18 by analysis of the EI-MS fragmentation of the amino derivative of its aglycone pentaacetate. Its absolute configuration was determined as 2S,3R,26S,27S by analysis of the 1H NMR and CD spectra of its aglycone pentabenzoate.
- Zhou, Bing-Nan,Mattern, Michael P,Johnson, Randall K,Kingston, David G.I
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- An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure–Activity Relationships
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The complexity of polymer–protein interactions makes rational design of the best polymer architecture for any given biointerface extremely challenging, and the high throughput synthesis and screening of polymers has emerged as an attractive alternative. A porphyrin-catalysed photoinduced electron/energy transfer–reversible addition-fragmentation chain-transfer (PET-RAFT) polymerisation was adapted to enable high throughput synthesis of complex polymer architectures in dimethyl sulfoxide (DMSO) on low-volume well plates in the presence of air. The polymerisation system shows remarkable oxygen tolerance, and excellent control of functional 3- and 4-arm star polymers. We then apply this method to investigate the effect of polymer structure on protein binding, in this case to the lectin concanavalin A (ConA). Such an approach could be applied to screen the structure–activity relationships for any number of polymer–protein interactions.
- Gormley, Adam J.,Yeow, Jonathan,Ng, Gervase,Conway, órla,Boyer, Cyrille,Chapman, Robert
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- Synthesis of C-Glycosyl Amino Acid Building Blocks Suitable for the Solid-Phase Synthesis of Multivalent Glycopeptide Mimics
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Five C-glycosyl functionalized lysine building blocks, featuring C-glycosidic derivatives of α-rhamnose, α-mannose, α-galactose, β-galactose, and β-N-acetyl glucosamine have been designed and synthesized. These derivatives, equipped with acid-labile protecting groups, are eminently suitable for solid-phase synthesis of multivalent glycopeptides. The lysine building blocks were prepared from C-allyl glycosides that underwent a Grubbs cross-metathesis with an acrylate, followed by a reduction of the C=C double bond in the resulting α,β-unsaturated esters, and liberation of the carboxylate to allow condensation with a lysine side chain. The thus obtained C-glycosides, five in total, were applied in the solid-phase peptide synthesis (SPPS) of three glycopeptides, showing the potential of the described building blocks in the assembly of well-defined mimics of homo- and heteromultivalent glycopeptides and glycoclusters.
- Reintjens, Niels R. M.,Koemans, Tony S.,Zilverschoon, Nick,Castelli, Riccardo,Cordfunke, Robert A.,Drijfhout, Jan Wouter,Meeuwenoord, Nico J.,Overkleeft, Herman S.,Filippov, Dmitri V.,van der Marel, Gijsbert A.,Codée, Jeroen D. C.
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- Selective binding of mannose-encapsulated gold nanoparticles to type 1 pili in Escherichia coli
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The synthesis, characterization and biological application of mannose encapsulated gold nanoparticles (m-AuNP) are reported. m-AuNP is well dispersed and very stable without aggregation in the media of broad ion strength and pH ranges. The selective binding of m-AuNP to the mannose adhesin FimH of bacterial type 1 pili is demonstrated using transmission electron microscopy. The competition assay with free mannose suggests that m-AuNP binds FimH better than free mannose does. This work demonstrates that carbohydrate attached nanoparticles can be used as an efficient affinity label and a multi-ligand carrier in a biological system. Copyright
- Lin, Chun-Cheng,Yeh, Yi-Chun,Yang, Chan-Yi,Chen, Chan-Long,Chen, Gee-Fong,Chen, Chia-Chun,Wu, Yi-Chun
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- 1:1 Adduct Ion Formation of Simple Carbohydrate Derivatives with Cations Using FAB Mass Spectrometry. Comparison of O-Acetyl, N-Butyl, and O-Methyl Modifications
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The 1:1 adduct ion formation between a series of per-O-acetylated aldopyranoses (family 1) or N-butylated glycosylamines (family 2) and an organic/metallic cation (n-C8H17NH3+/K+ or Li+) has been examined using quantitative FAB mass spectrometry.The per-O-acetyl modifications dramatically lead to negated selectivity of the carbohydrates toward the cation which has been clearly observed in per-O-methyl modifications.On the other hand, the mono-N-butyl modifications provide a similar selectivity pattern to mono-O-methyl ones.These results are understood on the basis of electronic and structural considerations.
- Sawada, Masami,Shizuma, Motohiro,Takai, Yoshio,Yamada, Hitoshi,Tanaka, Takanori,et al.
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- Formation of homooligosaccharides using base-promoted glycosylation of unprotected glycosyl fluorides
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Homooligomeric saccharides are of general interest with potential applications in chemical, pharmaceutical, and food industry as well as for materials with novel properties. This contribution describes a methodology of a base-promoted "single step self-oligomerization" of glycosyl fluorides as donors leading to oligomers with up to ~25 saccharide units. The influences of base and reaction time were examined. Linkage analysis of the corresponding alditol acetates by GC/MS allowed for calculation of average structural elements of oligomers.
- Steinmann, Andreas,Thimm, Julian,Matwiejuk, Martin,Thiem, Joachim
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- Mono-functionalized glycosylated platinum(IV) complexes possessed both pH and redox dual-responsive properties: Exhibited enhanced safety and preferentially accumulated in cancer cells in?vitro and in?vivo
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A serious of carbohydrate-conjugated platinum(IV) complexes in the form Pt(L2)(A2)(OH)R based on the clinical drug cisplatin and oxaliplatin were designed, synthesized and evaluated as antitumor agents in?vitro and in?vivo. The conjugates possessing both pH and redox dual-responsive properties exhibited more potent cytotoxicity in seven different human cancer cell lines and lower toxicity to the normal 3T3 cells than cisplatin, oxaliplatin and even the reported bis-functionalized glycosylated platinum(IV) complexes indicating the enhanced safety of the sugar conjugates. Cellular drug uptake and DNA platination were also superior to cisplatin, oxaliplatin and the reported bis-functionalized ones. Peak current of B7 and B8 with the scan rate of 200mv/s at the concentration of 0.08?mM was 5-fold higher at pH 6.4 than the pH 7.4, indicating that carbohydrate-conjugated mono-functionalized platinum(IV) complexes possessed both pH and redox dual-responsive properties in the cancer cells. The in?vivo assays demonstrated that the Pt(IV) compounds could inhibit the growth of MCF-7 tumour and exert more safety than oxaliplatin.
- Ma, Jing,Yang, Xiande,Hao, Wenpei,Huang, Zhonglv,Wang, Xin,Wang, Peng George
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- Synthesis of α-D-glucopyranosyl-(1-3)-α-D-mannopyranosyl-(1-7)-4- methylumbelliferone, a fluorogenic substrate for endo-α-1,2-mannosidase
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α-D-Glucopyranosyl-(1-3)-α-D-mannopyranosyl-(1-7)-4- methylumbelliferone (Glc-Man-Muf) was synthesized as a potential fluorogenic substrate for endo-α-1,2-mannosidase. The synthesis was designed in a convergent way. The glucose donor ethyl 2,3,4,6-tetra-O-benzyl-1-thio-β-glucopyranoside and the mannose acceptor 1,2:4,6-di-O-isopropylidene-β-D-mannopyranose were coupled in the presence of N-iodosuccinimide and trifluoromethane-sulfonic acid to yield the corresponding disaccharide derivative. After conversion into peracetylated α-D-glucopyranosyl-(1-3)-α-D-mannopyranose the disaccharide was attached to 4-methylumbelliferone using the Helferich method. After separation of the desired isomer, deacetylation yielded the title compound. Glc-Man-Muf was used as a substrate in endomannosidase assays with rat liver Golgi preparations as an enzyme source (in the presence of the α-glucosidase inhibitor deoxynojirimycin). The degradation of Glc-Man-Muf was linear with protein up to 300 μg and with time up to 2 h. Vmax and Km were determined to be 0.17 nmol/mg × h and 3.7 mM, respectively.
- Vogel,Pohlentz
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- Disaccharides as sialic acid aldolase substrates: Synthesis of disaccharides containing a sialic acid at the reducing end
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(Chemical Equation Presented) Synthesis with an unfussy enzyme: Escherichia coli sialic acid aldolase has been found to be unusually flexible in accepting disaccharides containing a mannose (Man) or N-glycolylmannosamine (ManNGc) at the reducing end as su
- Huang, Shengshu,Yu, Hai,Chen, Xi
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- Facile Preparation of per acetates and Per-3-bromobenzoates of α-Mono- And Disaccharides http://www.mdpi.org
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A simple and convenient method for the preparation of fully acetylated and (3-bromo)benzoylated α-monosaccharides and disaccharides through vigorous mechanical mixing of solid reactants on a high speed shaker is described. Using this technique a variety o
- Wang, Zerong,Matin, Mahfuza,Sheikh, Samia
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- Chlorotrimethylsilane catalysed acetylation of alcohols
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A variety of alcohols are converted into the corresponding acetates upon treatment with acetic anhydride and catalytic amount of chlorotrimethylsilane in acetonitrile (or dichloromethane).
- Kumareswaran,Gupta, Anuradha,Vankar, Yashwant D.
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- Tumor microenvironment responsive supramolecular glyco-nanovesicles based on diselenium-bridged pillar[5]arene dimer for targeted chemotherapy
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Supramolecular glyco-nanovesicles (SeSe-(P5)2?Man-NH3+) based on the host-guest complex of a diselenium-bridged pillar[5]arene dimer and a mannose derivative have been successfully developed for the first time, which possessed tumor microenvironment-respo
- Chen, Zelong,Hu, Xianjun,Jin, Ming,Pei, Yuxin,Pei, Zhichao,Pu, Liang,Wang, Yang
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- Potential anti-herpes and cytotoxic action of novel semisynthetic digitoxigenin-derivatives
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In recent years, new therapeutic possibilities were proposed for cardiac glycosides traditionally used to treat heart diseases, such as anticancer and antiviral activities. In this sense, this work aimed to synthesize the readily accessible 3β-azido-3-deoxydigitoxigenin (5) from digitoxigenin (1). Two new series of compounds were obtained from derivative (5): (i) O-glycosyl trizols through click chemistry with propargyl glycosides; and (ii) compounds substituted in the alpha carbonyl position with different residues linked via an amino-group. All obtained derivatives have their chemical structures confirmed, and their anti-herpes (against HSV-types 1 and 2 replication) and cytotoxic (against PC3, A549, HCT-8 and LNCaP cell lines) activities evaluated. Compounds 10 and 11 exhibited the most promising results against HSV-1 (KOS and 29-R strains) and HSV-2 (333 strain) replication with SI values > 1000. Both compounds were also the most cytotoxic for the human cancer cell lines tested with IC50 values similar to those of paclitaxel. They also presented reduced toxicity toward non-cancerous cell lines (MRC-5 and HGF cells). Promising compounds were tested in regard to their ability to inhibit Na+/K+-ATPase. The inhibition rate correlates suitably with the bioactivity demonstrated by those both compounds against the different human cancer cells tested as well as against HSV replication. Moreover, the results showed that specific chemical features of compound 10 and 11 influenced the bioactivities tested. In summary, it was possible to obtain novel digitoxigenin-derivatives with remarkable cytotoxic and anti-herpes activities as well as low toxicity and high selectivity. In this way, they could be considered potential molecules for the development of new drugs.
- Boff, Laurita,Munkert, Jennifer,Ottoni, Flaviano Melo,Zanchett Schneider, Naira Fernanda,Ramos, Gabriela Silva,Kreis, Wolfgang,Fernandes de Andrade, Saulo,Dias de Souza Filho, José,Braga, Fern?o Castro,Alves, Ricardo José,Maia de Pádua, Rodrigo,Oliveira Sim?es, Cláudia Maria
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- Silver Oxide Mediated Monotosylation of Poly(ethylene glycol) (PEG): Heterobifunctional PEG via Polymer Desymmetrization
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Heterobifunctional poly(ethylene glycol)s (PEGs) are key structures for bioconjugation in the context of the PEGylation strategy to enhance blood circulation times of, for example, peptide drugs or stealth liposomes. The formation of heterobifunctional PEGs from symmetric PEG diols is challenging because of limited yields of the targeted monofunctional product and difficulties associated with separation steps. On the basis of a detailed comparison of reaction conditions, we have investigated a polymer desymmetrization strategy to maximize the yields of monofunctional PEG tosylate. The tosylation reaction in the presence of the heterogeneous catalyst silver oxide and potassium iodide in a specific stoichiometric ratio proved to be highly efficient, resulting in 71-76% yield of monofunctional PEG depending on molecular weight, exceeding the expected value of 50% in a statistical reaction without addition of a catalyst. For characterization as well as for the preparative separation of monotosylated PEG, we developed a HPLC method, using an evaporative light scattering detector, enabling both analytical and semipreparative separation of monotosylated PEGs on gram scale up to 20 000 g mol-1. To demonstrate the efficiency of the procedure, an α-azido-ω-methacryloyl-PEG was prepared as a building block suitable for azide-alkyne click-type reactions that can be incorporated into polymer networks via radical polymerization. We click-functionalized α-azido-ω-methacryloyl-PEG with a mannose-functionalized alkyne to enable functionalization of nanogels for enhanced cellular uptake via the mannose receptor. The synthesis strategy is suitable for a broad range of applications in the field of PEGylation and for hydrogel and nanogel functionalization.
- Pohlit, Hannah,Worm, Matthias,Langhanki, Jens,Berger-Nicoletti, Elena,Opatz, Till,Frey, Holger
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- A Sweet H2S/H2O2Dual Release System and Specific Protein S-Persulfidation Mediated by Thioglucose/Glucose Oxidase
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H2S and H2O2 are two redox regulating molecules that play important roles in many physiological and pathological processes. While each of them has distinct biosynthetic pathways and signaling mechanisms, the crosstalk between these two species is also known to cause critical biological responses such as protein S-persulfidation. So far, many chemical tools for the studies of H2S and H2O2 have been developed, such as the donors and sensors for H2S and H2O2. However, these tools are normally targeting single species (e.g., only H2S or only H2O2). As such, the crosstalk and synergetic effects between H2S and H2O2 have hardly been studied with those tools. In this work, we report a unique H2S/H2O2 dual donor system by employing 1-thio-β-d-glucose and glucose oxidase (GOx) as the substrates. This enzymatic system can simultaneously produce H2S and H2O2 in a slow and controllable fashion, without generating any bio-unfriendly byproducts. This system was demonstrated to cause efficient S-persulfidation on proteins. In addition, we expanded the system to thiolactose and thioglucose-disulfide; therefore, additional factors (β-galactosidase and cellular reductants) could be introduced to further control the release of H2S/H2O2. This dual release system should be useful for future research on H2S and H2O2.
- Li, Xiaolu,Ni, Xiang,Qian, Wei-Jun,Shen, Tun-Li,Xian, Ming
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- A magnetic-nanoparticle-supported 4-N,N-dialkylaminopyridine catalyst: Excellent reactivity combined with facile catalyst recovery and recyclability
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(Figure Presented) Quick recovery: The first magnetic-nanoparticle- supported organocatalyst is prepared. The heterogeneous catalyst promotes a range of nucleophilic reactions and can be recovered by exposure to an external magnet (see picture). Furthermore, it can be recycled over 30 times without loss of activity.
- O Dalaigh, Ciaran,Corr, Serena A.,Gun'ko, Yurii,Connon, Stephen J.
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- Manipulation of free carbohydrates via stannylene acetals. Preparation of β-per-O-acyl derivatives of D-mannose, L-rhamnose, 6-O-trityl-D-talose, and D-lyxose
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A simple and high-yielding method for the preparation of 1-O-β-acyl derivatives of carbohydrates with an axial OH group at C-2 is described. It utilizes the property of unprotected carbohydrates to preferentially form 1,2-O-cis stannylene acetals, when tr
- Hodosi, Gyoergy,Kovac, Pavol
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- Solvent-free synthesis of decyl D-glycopyranosides under focused microwave irradiation
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A three step microwave assisted solvent-free synthesis of decyl D-glucopyranoside with 1-decanol was established for D-glucose and extended to D-galactose, D-mannose and N-troc-D-glucosamine with 70% average overall yield for the three steps (peracetylation, glycosylation and saponification). Rate enhancements and reduction of the reaction time were observed for the two last steps carried out under microwave irradiation when compared to conventional heating in the same conditions.
- Limousin,Cleophax,Petit,Loupy,Lukacs
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- Preparation and functional analysis of gossypols having two carbohydrate appendages with enaminooxy linkages
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We developed new gossypol (Gos)-based glycoconjugates through dehydration condensation of native Gos and chemically modified glycosides having aminooxy groups. The resultant glycoconjugates (glycoGos) were resistant to hydrolysis, although they were light-sensitive and slowly decomposed even under indoor lighting. The glycoGos also exhibited improved water solubility compared with native Gos, but their saturated concentrations in water were still low (6.4–17 μM), due to their hydrophobic naphthyl rings. We also carried out WST-8 assays to assess the anticancer activity of the glycoGos on DLD-1 and HepG2 cells and found that the glycoGos having β-lactosides and having β-galactosides (specific ligands for asialoglycoprotein receptors) showed enhanced anticancer activity on HepG2 cells.
- Amano, Yoshitsugu,Nakamura, Masaki,Shiraishi, Shinya,Chigira, Naoto,Shiozawa, Nobuya,Hagio, Masahito,Yano, Tomohiro,Hasegawa, Teruaki
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- A renewable, chemoselective, and quantitative ligand density microarray for the study of biospecific interactions
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Novel renewable microarray technology has been developed to immobilize and release carbohydrates and proteins from self-assembled monolayers (SAMs) of electroactive quinone-terminated alkanethiolates on gold surfaces. This method may be applied to a variety of research fields for use in biosensor technology and the generation of renewable and tailored microarrays for biospecific cell-based assays.
- Pulsipher, Abigail,Yousaf, Muhammad N.
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- Novel lipoamino acid- and liposaccharide-based system for peptide delivery: Application for oral administration of tumor-selective somatostatin analogues
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Lipoamino acid and liposaccharide conjugates of somatostatin analogue TT-232 were synthesized to modify the physicochemical properties of the parent peptide. The relative position, the number, and the nature of the lipid and/or saccharide moieties were varied. Experiments in vitro clearly showed that many compounds modified at the N- and/or C-terminus with lipid or sugar moieties retained the biological activity of the parent compound. An interesting construct was synthesized containing lipid and sugar units at opposite ends of the somatostatin analogue, so that the entire molecule could be considered as an amphipathic surfactant.
- Tóth, István,Malkinson, John P.,Flinn, Nicholas S.,Drouillat, Bruno,Horváth, Anikó,érchegyi, Judith,Idei, Miklós,Venetianer, Anikó,Artursson, Per,Lazorova, Lucia,Szende, Béla,Kéri, Gy?rgy
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- Solid silica sulfuric acid (SSA) as a novel and efficient catalyst for acetylation of aldehydes and sugars
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Acetylation of aldehydes and sugars catalyzed by solid silica sulfuric acid (SSA) is described. In these reactions SSA shows a highly catalytic nature: easy to handle procedure, short reaction time, recycle exploitation, insensitivity to air and moisture, excellent isolated yields. The catalyst could be recycled at least five times.
- Wu, Hui,Shen, Yang,Fan, Li-yan,Wan, Yu,Shi, Da-qing
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- Control of protein-binding kinetics on synthetic polymer nanoparticles by tuning flexibility and inducing conformation changes of polymer chains
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Although a number of procedures to create synthetic polymer nanoparticles (NPs) with an intrinsic affinity to target biomacromolecules have been published, little has been reported on strategies to control the binding kinetics of target recognition. Here,
- Hoshino, Yu,Nakamoto, Masahiko,Miura, Yoshiko
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- Glycosylated platinum(IV) prodrugs demonstrated significant therapeutic efficacy in cancer cells and minimized side-effects
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Conjugates (A1-A5) of the Pt(iv) derivative (A6) with amino groups from peracetyl glucose, rhamnose and mannose with a propyl amino or ethyl amino linker at the reducing end were synthesized and exhibited significant therapeutic efficacy in tumour cells, especially for prostate cancer (PCa). The antitumor activities are greatly affected by glycosyl groups. Cytotoxic experiments in vitro indicated that the antitumor activities were increased by 5-fold when its Pt(iv) derivative was conjugated to S18 (IC50 = 4.82 ± 0.45 μM) and by 12-fold when conjugated to S21 (IC50 = 1.9 ± 0.67 μM). The mannose substituted Pt(iv) complexes A4 and A5 were also over an order of magnitude more potent towards HeLa, A549, MCF-7 and PC3 than cisplatin and oxaliplatin. Importantly, the glycosylated Pt(iv) derivatives A4 and A5 displayed potential safety for clinical therapeutic exposure with IC50 of 84 μM and 169 μM compared with cisplatin (IC50 = 8 μM) to 3T3. Cellular uptake and DNA platination are higher than cisplatin and oxaliplatin. ESI-MS analysis of A5 binding to 5′-dGMP revealed that bifunctional DNA lesions were formed. The antitumor activities in vivo showed that the MTD and LD50 for A4 and A5 are nearly 4-fold higher than that of oxaliplatin indicating the potential safety for the glycosylated Pt(iv) complexes.
- Ma, Jing,Wang, Qingpeng,Yang, Xiande,Hao, Wenpei,Huang, Zhonglv,Zhang, Jiabao,Wang, Xin,Wang, Peng George
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- First total syntheses of four natural bioactive glucosides
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The efficient total syntheses of four biologically interesting natural glucosides Ethylconiferin, Butylconiferin, 2’-Butoxyethylconiferin and Balajaponin B, have been achieved for the first time starting from commercially available Vanilline via concise reaction sequence of 8–10 steps with the overall yield of 26–41%. This work definitely laid the foundation for the further pharmacological study of this kind of natural compounds. Meanwhile, currently developed approach could be used as a general synthetic strategy for the syntheses of other monolignol glucosides and their derivatives, and provides an opportunity for further study of the structure-activity relationship of this kind of glucosides.
- Xu, Guangya,Wu, Min,Yao, Zhongquan,Lou, Hongbin,Du, Weihong,Song, Mingwei,He, Yujiao,Dong, Hongbo
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- Facile and Versatile Chemoenzymatic Synthesis of Enterobactin Analogues and Applications in Bacterial Detection
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Siderophores, such as enterobactin (Ent), are small molecules that can be selectively imported into bacteria along with iron by cognate transporters. Siderophore conjugates are thus a promising strategy for delivering functional reagents into bacteria. In this work, we present an easy-to-perform, one-pot chemoenzymatic synthesis of functionalized monoglucosylated enterobactin (MGE). When functionalized MGE is conjugated to a rhodamine fluorophore, which affords RhB-Glc-Ent, it can selectively label Gram-negative bacteria that utilize Ent, including some E. coli strains and P. aeruginosa. V. cholerae, a bacterium that utilizes linearized Ent, can also be weakly targeted. Moreover, the targeting is effective under iron-limiting but not iron-rich conditions. Our results suggest that the RhB-Glc-Ent probe is sensitive not only to the bacterial strain but also to the iron condition in the environment.
- Lee, Albert A.,Chen, Yi -Chen S.,Ekalestari, Elisa,Ho, Sheng -Yang,Hsu, Nai -Shu,Kuo, Tang -Feng,Wang, Tsung -Shing Andrew
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- High throughput discovery of heteroaromatic-modifying enzymes allows enhancement of novobiocin selectivity
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Glycosylated analogues of novobiocin, discovered using a broad library of enzymes, have 100-fold improved activity against breast, brain, pancreatic, lung and ovarian cancers and ablated associated off-target activity leading to an up to 2.7 × 104 fold increase in selectivity.
- Patel, Sital M.,Fuente, Maria De La,Ke, Song,Guimaraes, Andreia M. R.,Oliyide, Adeola O.,Ji, Xiaoyun,Stapleton, Paul,Osbourn, Anne,Pan, Yi,Bowles, Dianna J.,Davis, Benjamin G.,Schatzlein, Andreas,Yang, Min
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- Synthesis and biological activities of galactose–aspirin conjugate prodrug designed for ADEPT and PMT
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Aspirin was used as the lead compound, and its structure was modified by galactosylation. Galactose-based aspirin prodrug was synthesized by using the α-d-glactopyranosyl bromide as glycosyl donor and aspirin as acceptor. The experimental method is simple and reproducible, has high yield and great practical value. The galactosylated aspirin prodrug was found to possess reduced cytotoxicity compared to aspirin, and selectively exhibited antiproliferative activity in the presence or in the absence of β-d-galactoside galactohydrolase with the approach of antibody-directed enzyme prodrug therapy (ADEPT) or the prodrug monotherapy (PMT).
- Huang, Gangliang
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- New ionic liquids from azepane and 3-methylpiperidine exhibiting wide electrochemical windows
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New ionic liquids based on azepanium and 3-methylpiperidinium cations have been synthesised; they exhibit moderate viscosities and remarkably wide electrochemical windows, thereby showing promise, inter alia, as electrolytes and battery materials, and as synthetic media.
- Belhocine, Tayeb,Forsyth, Stewart A.,Gunaratne, H. Q. Nimal,Nieuwenhuyzen, Mark,Puga, Alberto V.,Seddon, Kenneth R.,Srinivasan, Geetha,Whiston, Keith
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- Nonenzymatic synthesis of anomerically pure, mannosylbased molecular probes for scramblase identification studies
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The chemical synthesis of molecular probes to identify and study membrane proteins involved in the biological pathway of protein glycosylation is described. Two short-chain glycolipid analogs that mimic the naturally occurring substrate mannosyl phosphoryl dolichol exhibit either photoreactive and clickable properties or allow the use of a fluorescence readout. Both probes consist of a hydrophilic mannose headgroup that is linked to a citronellol derivative via a phosphodiester bridge. Moreover, a novel phosphoramidite chemistry-based method offers a straightforward approach for the non-enzymatic incorporation of the saccharide moiety in an anomerically pure form.
- Bütikofer, Peter,H?ner, Robert,Khorev, Oleg,Langenegger, Simon M.,Menon, Anant K.,Picca, Giovanni,Probst, Markus
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- A Bifunctional Spin Label for Ligand Recognition on Surfaces
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In situ monitoring of biomolecular recognition, especially at surfaces, still presents a significant technical challenge. Electron paramagnetic resonance (EPR) of biomolecules spin-labeled with nitroxides can offer uniquely sensitive and selective insights into these processes, but new spin-labeling strategies are needed. The synthesis and study of a bromoacrylaldehyde spin label (BASL), which features two attachment points with orthogonal reactivity is reported. The first examples of mannose and biotin ligands coupled to aqueous carboxy-functionalized gold nanoparticles through a spin label are presented. EPR spectra were obtained for the spin-labeled ligands both free in solution and attached to nanoparticles. The labels were recognized by the mannose-binding lectin, Con A, and the biotin-binding protein avidin-peroxidase. Binding gave quantifiable changes in the EPR spectra from which binding profiles could be obtained that reflect the strength of binding in each case.
- Hollas, Michael A.,Webb, Simon J.,Flitsch, Sabine L.,Fielding, Alistair J.
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- Fe2(SO4)3·xH2O-catalyzed per-O-acetylation of sugars compatible with acid-labile protecting groups adopted in carbohydrate chemistry
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Fully acetylated saccharides are inexpensive and very useful starting materials for the synthesis of many naturally occurring glycosides, oligosaccharides, and glycoconjugates. Ferric sulfate hydrate (Fe2(SO4)3·xH2O) was found to be a valuable Lewis acid promoter in the per-O-acetylation reaction of saccharides with acetic anhydride in 100% of conversion rate and 88-99% yields. Interestingly, the procedure is perfectly compatible with the presence of a variety of acid-labile protecting groups, such as isopropylidene, benzylidene, trityl, and TBDMS groups. The reactions were simply performed by stirring the mixture of a sugar with a slight excessive acetic anhydride in the presence of 2.0 mol % of Fe2(SO4)3·xH2O at rt and the pure products were obtained by a simple dilution of the reaction mixture with dichloromethane and washings with aqueous Na2CO3.
- Shi, Lei,Zhang, Guisheng,Pan, Feng
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- Synthesis of 4-methylumbelliferyl α-D-mannopyranosyl-(1→6)- β-D-mannopyranoside and development of a coupled fluorescent assay for GH125 exo-α-1,6-mannosidases
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Certain bacterial pathogens possess a repertoire of carbohydrate processing enzymes that process host N-linked glycans and many of these enzymes are required for full virulence of harmful human pathogens such as Clostridium perfringens and Streptococcus pneumoniae. One bacterial carbohydrate processing enzyme that has been studied is the pneumococcal virulence factor SpGH125 from S. pneumoniae and its homologue, CpGH125, from C. perfringens. These exo-α-1,6-mannosidases from glycoside hydrolase family 125 show poor activity toward aryl α-mannopyranosides. To circumvent this problem, we describe a convenient synthesis of the fluorogenic disaccharide substrate 4-methylumbelliferone α-d-mannopyranosyl-(1→6)-β-d- mannopyranoside. We show this substrate can be used in a coupled fluorescent assay by using β-mannosidases from either Cellulomonas fimi or Helix pomatia as the coupling enzyme. We find that this disaccharide substrate is processed much more efficiently than aryl α-mannopyranosides by CpGH125, most likely because inclusion of the second mannose residue makes this substrate more like the natural host glycan substrates of this enzyme, which enables it to bind better. Using this sensitive coupled assay, the detailed characterization of these metal-independent exo-α-mannosidases GH125 enzymes should be possible, as should screening chemical libraries for inhibitors of these virulence factors.
- Deng, Lehua,Tsybina, Polina,Gregg, Katie J.,Mosi, Renee,Zandberg, Wesley F.,Boraston, Alisdair B.,Vocadlo, David J.
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- PROCESS OF SYNTHESIS OF β-6'SULFOQUINOVOSYL DIACYLGLYCEROLS
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The present invention relates to a synthesis process of β-6-sulfoquinovosyl-diacylglycerols. In particular, said process is for the synthesis of the compounds 1,2-O-distearoyl-3-O-(β- sulfoquinovosyl)-R/S-glycerol, 1,2-O-distearoyl-3-O-(β-sulfoquinovosyl)-R-glycerol or 1,2- O-distearoyl-3-O-(β-sulfoquinovosyl)-S-glycerol, named respectively Sulfavant A, Sulfavant R and Sulfavant S.
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Page/Page column 11; 12
(2022/02/28)
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- Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity
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Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 μM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC50 0.4 μM) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program.
- Ahmed, Ajaz,Bhagat, Kavita,Choudhary, Sushil,Kaur Gulati, Harmandeep,Kumar, Ajay,Kumar, Nitish,Mukherjee, Debaraj,Singh Bedi, Preet Mohinder,Singh, Atamjit,Singh, Harbinder,Vir Singh, Jatinder
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- Synthesis and biological evaluation of 3β-O-neoglycosides of caudatin and its analogues as potential anticancer agents
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In order to study the structure–activity relationship (SAR) of C21-steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3β-O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3β-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3β-O-(2,3,4-tri-O-acetyl-β-L-glucopyranosyl)-caudatin (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC50 value of 3.11 μM. Mechanical studies showed that compound 2k induced both apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve anticancer activity for naturally occurring C21-steroidal aglycones, and compound 2k represents a potential anticancer agent deserved further investigation.
- Li, Xiao-San,Chen, Tang-Ji,Xu, Zhi-Peng,Long, Juan,He, Miao-Ying,Zhan, He-Hui,Zhuang, Hai-Cai,Wang, Qi-Lin,Liu, Li,Yang, Xue-Mei,Tang, Jin-Shan
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- Selectivity of 1-O-Propargyl-D-Mannose Preparations
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Thanks to their ability to bind to specific biological receptors, mannosylated structures are examined in biomedical applications. One of the most common ways of linking a functional moiety to a structure is to use an azide-alkyne click reaction. Therefore, it is necessary to prepare and isolate a propargylated mannose derivative of high purity to maintain its bioactivity. Three known preparations of propargyl-α-mannopyranoside were revisited, and products were analysed by NMR spectroscopy. The preparations were shown to yield by-products that have not been described in the literature yet. Our experiments showed that one-step procedures could not provide pure propargyl-α-mannopyranoside, while a three-step procedure yielded the desired compound of high purity.
- ?ezanka, Michal,Dolensky, Bohumil,Krabicová, Ilona
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- Inhibition of S. aureus Infection of Human Umbilical Vein Endothelial Cells (HUVECs) by Trehalose- and Glucose-Functionalized Gold Nanoparticles
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Microbial adhesion to host cells represents the initial step in the infection process. Several methods have been explored to inhibit microbial adhesion including the use of glycopolymers based on mannose, galactose, sialic acid and glucose. These sugar re
- Li, Yimeng,Ariotti, Nicholas,Aghaei, Behnaz,Pandzic, Elvis,Ganda, Sylvia,Willcox, Mark,Sanchez-Felix, Manuel,Stenzel, Martina
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supporting information
p. 22652 - 22658
(2021/09/13)
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- Chemical Synthesis and Biological Evaluations of Adiponectin Collagenous Domain Glycoforms
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The homogeneously glycosylated 76-amino acid adiponectin collagenous domains (ACDs) with all of the possible 15 glycoforms have been chemically and individually synthesized using stereoselective glycan synthesis and chemical peptide ligation. The following biological and pharmacological studies enabled correlating glycan pattern to function in the inhibition of cancer cell growth as well as the regulation of systemic energy metabolism. In particular, hAdn-WM6877 was tested in detail with different mouse models and it exhibited promising in vivo antitumor, insulin sensitizing, and hepatoprotective activities. Our studies demonstrated the possibility of using synthetic glycopeptides as the adiponectin downsized mimetic for the development of novel therapeutics to treat diseases associated with deficient adiponectin.
- Wu, Hongxiang,Zhang, Yiwei,Li, Yuanxin,Xu, Jianchao,Wang, Yu,Li, Xuechen
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supporting information
p. 7808 - 7818
(2021/05/26)
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- Total synthesis of three natural phenethyl glycosides
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Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.
- Dong, Hong-Bo,Meng, Jian,Yao, Zhong-Quan,Luo, Hong-Bing,Zhang, Jing-Xia,Du, Wei-Hong,Tang, Ke-Hui,Cao, Sheng-Hua
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p. 284 - 293
(2020/03/03)
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- An alternative approach for the synthesis of sulfoquinovosyldiacylglycerol
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Sulfoquinovosyldiacylglycerol (SQDG) is a glycolipid ubiquitously found in photosyn-thetically active organisms. It has attracted much attention in recent years due to its biological ac-tivities. Similarly, the increasing demand for vegan and functional foods has led to a growing interest in micronutrients such as sulfolipids and their physiological influence on human health. To study this influence, reference materials are needed for developing new analytical methods and providing enough material for model studies on the biological activity. However, the availability of these materials is limited by the difficulty to isolate and purify sulfolipids from natural sources and the unavailability of chemical standards on the market. Consequently, an alternative synthetic route for the comprehensive preparation of sulfolipids was established. Here, the synthesis of a sulfolipid with two identical saturated fatty acids is described exemplarily. The method opens possibilities for the preparation of a diverse range of interesting derivatives with different saturated and unsatu-rated fatty acids.
- Domey, Hendrik,Fischer, Judith,Rohn, Sascha,Sitz, Tobias
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- First total syntheses of two natural glycosides
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Isosyringinoside (1) and 3-(O-β-D-glucopyranosyl)-α-(O-β-D-glucopyranosyl)-4-hydroxy phenylethanol (2), the natural bioactive compounds contained unique structures, were first totally synthesized using easily available materials in short convenient routes with overall yields of 20.2% and 27.0%, respectively. An efficient total synthesis of 1 was developed in six steps, which contained two key steps of highly regioselective glycosylation without any selective protection steps. The seven-step synthesis of 2 involved two steps of regioselective glycosylations using BF3–O(C2H5)2 and TMSOTf as catalysts, respectively.
- Dong, Hongbo,Du, Weihong,Yao, Zhongquan,Wu, Min,Luo, Hongbing,He, Yujiao,Cao, Shenghua
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supporting information
(2020/12/02)
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- Preparation and formulation optimization of methotrexate-loaded human serum albumin nanoparticles modified by mannose
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Background: Methotrexate (MTX) is the representative drug among the dis-ease-modifying anti-rheumatic drugs. However, the conventional treatment with MTX showed many limitations and side effects. Objective: To strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which are referred to as MTX-M-NPs. Methods: Firstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by the method of central composite design (CCD), with the drug lipid ra-tio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. The response of different formulations was calculated, and the response surface diagram, con-tour diagram, and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neu-trophils was studied through confocal laser detection. Further, MTX-M-NPs were subject-ed to assessment of the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats. Results: This targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized for-mula, MTX-M-NPs were prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could pro-long the in vivo circulation time of MTX. Conclusion: This targeting drug delivery system laid a promising foundation for the treatment of RA.
- Chen, Zhenyu,Luo, Zhongling,Lyu, Jiayao,Wang, Jianxin,Liu, Zhongbing,Wei, Jun,Lin, Yan,Zhong, Zhirong
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p. 5016 - 5029
(2021/08/17)
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- Does targeting Arg98 of FimH lead to high affinity antagonists?
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Bacterial resistance has become an important challenge in the treatment of urinary tract infections. The underlying resistance mechanisms can most likely be circumvented with an antiadhesive approach, antagonizing the lectin FimH located at the tip of fim
- Toma?i?, Tihomir,Rabbani, Said,Jakob, Roman P.,Reisner, Andreas,Jakopin, ?iga,Maier, Timm,Ernst, Beat,Anderluh, Marko
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- Amino acid derivative and preparation method thereof
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The invention discloses an amino acid derivative and a preparation method thereof. The amino acid comprises - SH and/or - OH groups, wherein the sugar chain comprises one mannose or more than two mannose in series, and the linker comprises S or o, the method of the invention can synthesize the required polysaccharide compound in one step, thereby not only saving a large amount of manpower and time, but also enabling a large amount of preparation of the target compound to be smooth. , The synthesis yield of the product is improved, a large amount of synthetic raw materials are saved, the production cost is greatly reduced, meanwhile, the environmental protection is facilitated, and the research of amino acid glycosylation is broken through and the application barrier is applied.
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Paragraph 0056-0060
(2021/10/11)
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- Preparation and characterization of glycopolymers with biphenyl spacers: Via Suzuki coupling reaction
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Poly(vinylbiphenyl)s bearing glycoside ligands at the side chains were prepared using the Suzuku coupling reaction. Effects of glycoside reactant concentration, halide species, glycoside species, and catalyst species on the incorporation of glycoside ligand into the polymer were investigated. The obtained glycopolymers exhibited specific binding to proteins corresponding to the glycoside ligands. In addition, the biphenyl spacers formed by the Suzuki coupling reaction in the glycopolymer were fluorescent, whereas the polymer precursor was not.
- Seto, Hirokazu,Tono, Takumi,Nagaoka, Akiko,Yamamoto, Mai,Hirohashi, Yumiko,Shinto, Hiroyuki
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supporting information
p. 4474 - 4477
(2021/05/31)
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- CuAAC mediated synthesis of cyclen cored glycodendrimers of high sugar tethers at low generation
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Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, pharmaceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems. Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to produce a variety of novel 12–sugar coated (G0) glycodendrimers 12-15 adorn with β-Glc-, β-Man-, β-Gal-, β-Lac, along with 36-galactose coated (G1) glycodendrimer 18 in good-to-high yield. The structures of the developed glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR (1H & 13CNMR), HRMS, MALDI-TOF MS, UV–Vis, IR, and SEC (Size Exclusion Chromatogram) data.
- Agrahari, Anand K.,Jaiswal, Manoj K.,Yadav, Mangal S.,Tiwari, Vinod K.
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- Mannose-modified azide exosome and application thereof
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The invention belongs to the field of biological medicine, and particularly relates to a mannose-modified azide exosome and an application thereof. The mannose-modified azide exosome is prepared through metabolic labeling and click chemistry reaction; the advantages of the surface-functionalized azide exosome targeting macrophages are determined through a flow cytometry on the cellular level, and in-vitro pharmacological experiments prove that the mannose-modified azide exosome has the advantage of treating infectious diseases after being loaded with drugs. According to the surface-functionalized azide exosome provided by the invention, the targeting property of the exosome as a drug carrier can be greatly improved, and the effect of the surface-functionalized azide exosome in treating refractory infectious related diseases is improved.
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Paragraph 0056; 0062-0064
(2021/06/23)
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- Synthesis of Glycosyl Fluorides by Photochemical Fluorination with Sulfur(VI) Hexafluoride
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This study describes a new convenient method for the photocatalytic generation of glycosyl fluorides using sulfur(VI) hexafluoride as an inexpensive and safe fluorinating agent and 4,4′-dimethoxybenzophenone as a readily available organic photocatalyst. This mild method was employed to generate 16 different glycosyl fluorides, including the substrates with acid and base labile functionalities, in yields of 43%-97%, and it was applied in continuous flow to accomplish fluorination on an 7.7 g scale and 93% yield.
- Bannykh, Anton,Khomutnyk, Yaroslav,Kim, Sungjin,Nagorny, Pavel
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supporting information
p. 190 - 194
(2021/01/13)
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- Protecting carbohydrates with ethers, acetals and orthoesters under basic conditions
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Chlorinated ethyl and vinyl ethers are introduced at various positions of carbohydrates. Depending on the relative stereochemistry, vinylethers, acetals or orthoesters are formed under basic conditions. The products are stable, but are easily deprotected
- Liang, Yang,Pedersen, Christian M.
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supporting information
p. 7598 - 7601
(2021/09/22)
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- Isolation and characterization of triterpenoid saponins from leaves of Aralia nudicaulis L
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Three new oleanolic glycosides (1–3), along with seven known saponins from various plants (4–10) were isolated for the first time from the leaves of Aralia nudicaulis. Their structures were elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR, and HRESIMS. Nudicauloside A and B (1–2) have shown moderate anti-inflammatory activity, as demonstrated by inhibition of LPS-induced NO production in raw 264.7 murine macrophages (IC50 = 74–101 μM).
- Lavoie, Serge,Pierra, Julie,Legault, Jean,Raminoson, Diamondra,Lion, Quentin,Mshvildadze, Vakhtang,Pichette, André
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p. 184 - 189
(2021/04/23)
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- Substituted pyrazole compound, preparation method, pharmaceutical composition and applications thereof
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The invention discloses a substituted pyrazole compound represented by a formula I, and a preparation method, a pharmaceutical composition and applications thereof, wherein the compound has characteristics of good stability, excellent solubility, low cytotoxicity and remarkable neuroprotective effect, can effectively prevent and treat nerve cell injury, and is an ideal medicinal compound for preventing or treating cerebral stroke, cerebral embolism, cerebral stroke sequelae, cerebral stroke dyskinesia, mitochondrial encephalomyopathy and amyotrophic lateral sclerosis of spinal cord.
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Paragraph 0270-0275
(2020/03/12)
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- Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
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In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential.
- Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
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- Short gram-scale synthesis of sulfavant A
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Recently, we reported the promising activity of a novel class of sulfoquinovosyl-diacylglycerols named Sulfavants as molecular vaccine adjuvants. Herein, we describe a modified and improved chemical synthesis of the lead product Sulfavant A (1), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical development. Starting from the versatile synthesis based on the trichloroacetimidate methodology, up-scaled preparation of Sulfavant A (1) was achieved in 11 steps by elimination and modification of those reactions that negatively affected the overall yield by the previous procedure. The novel strategy gave 17% overall yield of the target compound 1 and also paved the way for the gram-scale preparation of a wide range of other charged and neutral glycoglycerolipids.
- Ziaco, Marcello,Fioretto, Laura,Nuzzo, Genoveffa,Fontana, Angelo,Manzo, Emiliano
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p. 2728 - 2733
(2020/11/18)
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- Tea leaf perfumery precursor glucoside and synthesizing method thereof
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The invention relates to a tea leaf perfumery precursor glucoside and a synthesizing method thereof. The synthesizing method comprises the following steps of synthesizing ten glucosides including aromatic alcohol ( alkanol )-beta -D-glucosides and aromatic alcohol (alkanol )-beta -D-primrose indicans. The synthesizing method disclosed by the invention is a glucoside synthesizing method which is good in selectivity, high in production rate and low in cost.
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Paragraph 0044-0049
(2020/07/02)
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- Carbonyl compound containing amino acid connecting chain or pharmaceutically acceptable salt thereof, and preparation method and application of carbonyl compound
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The invention provides a carbonyl compound containing an amino acid connecting chain or a pharmaceutically acceptable salt thereof as well as a preparation method and application of the carbonyl compound, and belongs to the technical field of anti-AIDS medicines. The carbonyl compound containing the amino acid connecting chain or the pharmaceutically acceptable salt thereof provided by the invention has a structure shown as formula I in the specification. The carbonyl compound containing the amino acid connecting chain or the pharmaceutically acceptable salt thereof provided by the inventionhas obvious activity of inhibiting HIV protease; the obvious inhibition activity is realized on the DRV drug-resistant strain; toxicity research shows that the compound is low in toxicity and has gooddruggability; the inhibitory activity on HIV-1 protease is 286-1052 times of the inhibitory activity of a positive control drug DRV on HIV-1 protease; the inhibitory activity on a DRV drug-resistantstrain and the inhibitory activity on a wild HIV-1 drug-resistant strain are only reduced by 1.10-3.23 times, and the compound has a good application prospect as an anti-AIDS drug.
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Paragraph 0215; 0224-0226
(2020/06/16)
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- Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis
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Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.
- Li, Zhihao,Bavaro, Teodora,Tengattini, Sara,Bernardini, Roberta,Mattei, Maurizio,Annunziata, Francesca,Cole, Richard B.,Zheng, Changping,Sollogoub, Matthieu,Tamborini, Lucia,Terreni, Marco,Zhang, Yongmin
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supporting information
(2020/07/27)
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- Preparation method of 3, 4, 6-O-triacetyl-D-glucal
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The invention relates to a preparation method of Tri-O-acetyl-D-glucal, which mainly solves the problems of volatile reagent, irritant smell, high cost and the like in the existing method. The technical scheme of the invention is as follows: the preparation method of 3, 4, 6-O-triacetyl-D-glucal comprises the following steps: peracetylated D-glucose is prepared by catalyzing D-glucose in glacial acetic acid with strong acid; the peracetylated D-glucose is brominated by a glacial acetic acid solution of hydrogen bromide to obtain brominated peracetylated D-glucose; and the brominated peracetylated D-glucose is reduced by zinc powder in an ammonium chloride solution to obtain a final product 3, 4, 6-O-triacetyl-D-glucal. The product provided by the invention has important application in thefields of glycopeptides and other polypeptide drugs.
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Paragraph 0012-0014
(2020/05/14)
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- Studies on the stereoselective synthesis and immunosuppressive activity of dihydroartemisinin-O-glycoside derivatives
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Eight new dihydroartemisinin-O-glycosides were synthesized with their relative configurations were determined based on NMR spectrum. In vitro immunosuppressive assay showed that 10α-dihydroartemisinin-β-O-D-mannoside (19a) demonstrate 88percent inhibition towards T cells proliferation and 98percent reduction in IFN-γ levels in cell media. These results suggest that dihydroartemisinin-O-glycoside as a potential lead for further in vivo evaluation.
- Bian, Hongzhu,Dong, Xun,Shen, Zhengwu,Xu, Wei,Yu, Jingfeng,Yu, Yu,Zhang, Jinghua,Zou, Xiaosu
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supporting information
(2020/07/21)
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- Total Synthesis of Phospholipomannan of Candida albicans
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First, total synthesis of the cell surface phospholipomannan anchor [β-Manp-(1 → 2)-β-Manp]n-(1 → 2)-β-Manp-(1 → 2)-α-Manp-1 → P-(O → 6)-α-Manp-(1 → 2)-Inositol-1-P-(O → 1)-phytoceramide of Candida albicans is reported. The target phospholipomannan (PLM) anchor poses synthetic challenges such as the unusual kinetically controlled (1 → 2)-β-oligomannan domain, anomeric phosphodiester, and unique phytoceramide lipid tail linked to the glycan through a phosphate group. The synthesis of PLM anchor was accomplished using a convergent block synthetic approach using three main appropriately protected building blocks: (1 → 2)-β-tetramannan repeats, pseudodisaccharide, and phytoceramide-1-H-phosphonate. The most challenging (1 → 2)-β-tetramannan domain was synthesized in one pot using the preactivation method. The phytoceramide-1-H-phosphonate was synthesized through an enantioselective A3 three-component coupling reaction. Finally, the phytoceramide-1-H-phosphonate moiety was coupled with pseudodisaccharide followed by deacetylation to produce the acceptor, which on subsequent coupling with tetramannosyl-H-phosphonate provided the fully protected PLM anchor. Final deprotection was successfully achieved by Pearlman's hydrogenation.
- Ali, Asif,Gannedi, Veeranjaneyulu,Singh, Parvinder Pal,Vishwakarma, Ram A.
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p. 7757 - 7771
(2020/07/25)
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- GLUCOSAMINE DERIVATIVES AND PHARMACEUTICAL USES THEREOF
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There are provided compounds of Formula (A) and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, used for the prevention or treatment in a mammal of joint and bone disorders such as arthritis and osteoporosis.
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Paragraph 0209
(2019/07/03)
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- Synthesis and biological evaluation of some novel S-β-D-glucosides of 4-amino-5-alkyl-1,2,4-triazole-3-thiones derivatives
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A novel series of 3-S-β-D-glucosides-4-arylideneamino-5-alkyl-1,2,4-triazoles were designed and synthesized by reaction of 4-amino-5-alkyl-4H-1,2,4triazole-3-thiol Schiff bases and 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide. The structures of the target compounds have been characterized by 1H NMR, 13C NMR, FT-IR, and Microanalyses. All the newly synthesized compounds have been screened for their in vitro antibacterial and antifungal activities against two Gram-positive bacteria [Bacillus cereus (PTCC 1015) and Staphylococcus aureus (ATCC 25923)], two Gram-negative bacteria [Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (PTCC 1399) and two fungi [Aspergillus Niger (PTCC 5012) and Candida albicans (PTCC 5027)].
- Aghkand, Anila Rahimi,Dilmaghani, Karim Akbari,Ghezelbash, Zahra Dono,Asghari, Behvar
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p. 344 - 350
(2019/07/22)
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- Preparation method of 6-bromo-D-glucal
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The invention discloses a preparation method of 6-bromo-D-glucal. The reaction route is as follows. The preparation method comprises the following steps: (1), taking glucose as an initial material, and performing reaction in a sodium acetate/acetic anhydride system, so as to form a compound 1; (2), ensuring that the compound 1 is reacted with hydrobromic acid in acetic acid in a methylene dichloride system, so as to form a compound 2; (3), ensuring that the compound 2 is reacted with zinc powder in an acetone/saturated sodium dihydrogen phosphate, so as to form a compound 3; (4), ensuring thatthe compound 3 is reacted in a methanol/sodium methylate system, so as to form D-glucal, and then ensuring that the compound 3 is sequentially reacted with TsCl and acetic anhydride in a pyridine/methylene dichloride system, so as to form a compound 4; (5), ensuring that the compound 4 is reacted with LiBr in a DMSO system, so as to form a compound 5; (6), ensuring that the compound 5 is reacteda the sodium methylate/methanol system, so as to form a compound 6. The preparation method is simple to operate, mild in reaction conditions, cheap and available in raw materials, high in yield, low in cost, and suitable for mass industrial production.
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Paragraph 0024; 0025; 0026; 0027
(2019/02/26)
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- Glucose-conjugated platinum(IV) complexes as tumor-targeting agents: design, synthesis and biological evaluation
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A new series of glucose-conjugated Pt(IV) complexes that target tumor-specific glucose transporters (GLUTs) was designed, synthesized, and evaluated for their anticancer activities. All six compounds, namely, A1-A6, exhibited increased cytotoxicity that w
- Wang, Haifeng,Yang, Xiande,Zhao, Caili,Wang, Peng George,Wang, Xin
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supporting information
p. 1639 - 1645
(2019/03/08)
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- Phosphotungstic acid as a novel acidic catalyst for carbohydrate protection and glycosylation
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This work demonstrates the utilization of phosphotungstic acid (PTA) as a novel acidic catalyst for carbohydrate reactions, such as per-O-acetylation, regioselective O-4,6 benzylidene acetal formation, regioselective O-4 ring-opening, and glycosylation. These reactions are basic and salient during the synthesis of carbohydrate-based bioactive oligomers. Phosphotungstic acid's high acidity and eco-friendly character make it a tempting alternative to corrosive homogeneous acids. The various homogenous acid catalysts were replaced by the phosphotungstic acid solely for different carbohydrate reactions. It can be widely used as a catalyst for organic reactions as it is thermally stable and easy to handle. In our work, the reactions are operated smoothly under ambient conditions; the temperature varies from 0 °C to room temperature. Good to excellent yields were obtained in all four kinds of reactions.
- Chen, Jyun-Siao,Sankar, Arumugam,Lin, Yi-Jyun,Huang, Po-Hsun,Liao, Chih-Hsiang,Wu, Shen-Shen,Wu, Hsin-Ru,Luo, Shun-Yuan
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p. 33853 - 33862
(2019/11/11)
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- Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection
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Leishmaniasis, a neglected tropical disease, currently infects approximately 12 million people worldwide with 1 to 2 million new cases each year in predominately underdeveloped countries. The treatment of the disease is severely underdeveloped due to the
- Rintelmann, Chelsea L.,Grinnage-Pulley, Tara,Ross, Kathleen,Kabotso, Daniel E.K.,Toepp, Angela,Cowell, Anne,Petersen, Christine,Narasimhan, Balaji,Pohl, Nicola
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supporting information
p. 623 - 632
(2019/04/17)
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- CuII and AuIII Complexes with Glycoconjugated Dithiocarbamato Ligands for Potential Applications in Targeted Chemotherapy
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This work is focused on the synthesis, characterization, and preliminary biological evaluation of bio-conjugated AuIII and CuII complexes with the aim of overcoming the well-known side effects of chemotherapy by improving the selective accumulation of an anticancer metal payload in malignant cells. For this purpose, carbohydrates were chosen as targeting agents, exploiting the Warburg effect that accounts for the overexpression of glucose-transporter proteins (in particular GLUTs) in the phospholipid bilayer of most neoplastic cells. We linked the dithiocarbamato moiety to the C1 position of three different monosaccharides: d-glucose, d-galactose, and d-mannose. Altogether, six complexes with a 1:2 metal-to-ligand stoichiometry were synthesized and in vitro tested as anticancer agents. One of them showed high cytotoxic activity toward the HCT116 colorectal human carcinoma cell line, paving the way to future in vivo studies aimed at evaluating the role of carbohydrates in the selective delivery of whole molecules into cancerous cells.
- Pettenuzzo, Nicolò,Brustolin, Leonardo,Coltri, Elisa,Gambalunga, Alberto,Chiara, Federica,Trevisan, Andrea,Biondi, Barbara,Nardon, Chiara,Fregona, Dolores
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p. 1162 - 1172
(2019/05/27)
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- Sugar molecules coupled diketopyrrolo pyrrole compound and its preparation method
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The invention relates to a novel sugar molecule coupled diketopyrrolopyrrole compound with a general formula shown as (I). Specifically, R1 is H, Br, Cl, F, CN, C1-8 straight chain or branched alkyl,substituted or unsubstituted aromatic alkyl, C1-8 straight chain or branched alkoxy, C1-8 mono-substituted or disubstituted amino; A is monoglycosyl, diglycosyl or triglycosyl; and B is H or monoglycosyl, diglycosyl or triglycosyl identical to A. The invention also relates to a preparation method of the compound.
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Paragraph 0043-0049
(2019/10/29)
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- MONOSACCHARIDE PHOSPHORAMIDATE PRODRUGS
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The present disclosure provides monosaccharide phosphoramidate prodrugs of monosaccharide monophosphates. The present disclosure further provides methods of treating diseases of conditions such as congenital disorders of glycosylation comprising administering the monosaccharide phosphoramidate prodrugs of the present disclosure to a patient in need thereof.
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Paragraph 0149; 0175
(2019/07/19)
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- Synthesis method of core structure of O-mannan
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The invention belongs to the field of synthesis of saccharide substances, and particularly relates to a synthesis method of the core structure of O-mannan. Conventional research indicates that alpha-DG O-mannan is relevant with a mechanism of diseases of
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Paragraph 0104; 0114; 0115
(2019/08/06)
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- VANCOMYCIN DERIVATIVE, PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
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Provided are a class of vancomycin derivatives with a structure as shown in the general formula below and pharmaceutically acceptable salts thereof, a preparation method, a pharmaceutical composition containing the compound thereof, and the use of these compounds in preparing drugs for treating and/or preventing bacterial infection diseases, in particular drugs for treating infection diseases caused by Gram-positive bacteria.
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Paragraph 0041; 0051; 0052
(2019/03/13)
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- Chemoenzymatic Synthesis of C6-Modified Sugar Nucleotides to Probe the GDP- d -Mannose Dehydrogenase from Pseudomonas aeruginosa
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The chemoenzymatic synthesis of a series of C6-modified GDP-d-Man sugar nucleotides is described. This provides the first structure-function tools for the GDP-d-ManA producing GDP-d-mannose dehydrogenase (GMD) from Pseudomonas aeruginosa. Using a common C6 aldehyde functionalization strategy, chemical synthesis introduces deuterium enrichment, alongside one-carbon homologation at C6 for a series of mannose 1-phosphates. These materials are shown to be substrates for the GDP-mannose pyrophosphorylase from Salmonella enterica, delivering the required toolbox of modified GDP-d-Mans. C6-CH3 modified sugar-nucleotides are capable of reversibly preventing GDP-ManA production by GMD. The ketone product from oxidation of a C6-CH3 modified analogue is identified by high-resolution mass spectrometry.
- Ahmadipour, Sanaz,Pergolizzi, Giulia,Rejzek, Martin,Field, Robert A.,Miller, Gavin J.
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supporting information
p. 4415 - 4419
(2019/06/17)
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- Visible Light Enables Aerobic Iodine Catalyzed Glycosylation
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A versatile protocol for light induced catalytic activation of thioglycosides using iodine as an inexpensive and readily available photocatalyst was developed. Oxygen serves as a green and cost-efficient terminal oxidant and irradiation is performed with a common household LED-bulb. The scope of this glycosylation protocol was investigated in the synthesis of O-glycosides with yields up to 95 %.
- Krumb, Matthias,Lucas, Tobias,Opatz, Till
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supporting information
p. 4517 - 4521
(2019/08/06)
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- The effect of monosaccharides on self-assembly of benzenetricarboxamides
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The interaction between monosaccharides exhibits an important role in the assembly of monosaccharide-containing molecules. In this work, three common monosaccharides, glucose, galactose and mannose, are employed to investigate the effect of monosaccharide on the self-assembly of benzenetricarboxamide (BTA) core-containing molecules. In the presence of monosaccharides, three benzenetricarboxamide derivatives aggregate into different ordered structures. When alanine linkers are introduced to these molecules between the core and the monosacchride, morphologies of three types of monosaccharide BTAs turned to disordered, meanwhile their structures become similar with the increase of the length of alanine linkers, indicating the disappearance of the monosaccharide effects.
- Wang, Jue,Qi, Wenjing,Chen, Guosong
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supporting information
p. 587 - 591
(2019/01/04)
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- Extra Sugar on Vancomycin: New Analogues for Combating Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci
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Lipophilic substitution on vancomycin is an effective strategy for the development of novel vancomycin analogues against drug-resistant bacteria by enhancing bacterial cell wall interactions. However, hydrophobic structures usually lead to long elimination half-life and accumulative toxicity; therefore, hydrophilic fragments were also introduced to the lipo-vancomycin to regulate their pharmacokinetic/pharmacodynamic properties. Here, we synthesized a series of new vancomycin analogues carrying various sugar moieties on the seventh-amino acid phenyl ring and lipophilic substitutions on vancosamine with extensive structure-activity relationship analysis. The optimal analogues indicated 128-1024-fold higher activity against methicillin-susceptible S. aureus, vancomycin-intermediate resistant S. aureus (VISA), and vancomycin-resistant Enterococci (VRE) compared with that of vancomycin. In vivo pharmacokinetics studies demonstrated the effective regulation of extra sugar motifs, which shortened the half-life and addressed concerns of accumulative toxicity of lipo-vancomycin. This work presents an effective strategy for lipo-vancomycin derivative design by introducing extra sugars, which leads to better antibiotic-like properties of enhanced efficacy, optimal pharmacokinetics, and lower toxicity.
- Guan, Dongliang,Chen, Feifei,Xiong, Lun,Tang, Feng,Faridoon,Qiu, Yunguang,Zhang, Naixia,Gong, Likun,Li, Jian,Lan, Lefu,Huang, Wei
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supporting information
p. 286 - 304
(2018/02/10)
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