- 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
-
-
- Synthesis of malformin-A1, C, a glycan, and an aglycon analog: Potential scaffolds for targeted cancer therapy
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Improvement in therapeutic efficacy while reducing chemotherapeutic side effects remains a vital objective in synthetic design for cancer treatment. In keeping with the ethos of therapeutic development and inspired by the Warburg effect for augmenting biological activities of the malformin family of cyclic-peptide natural products, specifically anti-tumor activity, a β-glucoside of malformin C has been designed and synthesized utilizing precise glycosylation and solution phase peptide synthesis. We optimized several glycosylation procedures utilizing different donors and acceptors. The overarching goal of this study was to ensure a targeted delivery of a glyco-malformin C analog through the coupling of D-glucose moiety; selective transport via glucose transporters (GLUTs) into tumor cells, followed by hydrolysis in the tumor microenvironment releasing the active malformin C a glycon analog. Furthermore, total synthesis of malformin C was carried out with overall improved strategies avoiding unwanted side reactions thus increasing easier purification. We also report on an improved solid phase peptide synthesis protocol for malformin A1.
- Andreana, Peter R.,Hossain, Farzana,Nishat, Sharmeen
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-
- Synthesis of podophyllotoxin-glycosyl triazoles via click protocol mediated by silver (I)-N-heterocyclic carbenes and their anticancer evaluation as topoisomerase-II inhibitors
-
Herein we report the regioselective synthesis of podophyllotoxin-Glycosyl triazole hybrids catalysed by Ag(I)-N-heterocyclic carbene (Ag(I)-NHC) in a short reaction time (~30 min) at ambient conditions. In principle, it is the first report of Click alkyne-azide cycloaddition catalysed by Ag(I)-NHC catalyst and moreover, this new methodology yielded good results when compared with traditional CuAAC in terms of reaction time and selectivity. The synthesised compounds were further explored for in vitro anticancer activity against four human cancer cell lines Du145, HeLa, A-549, and MCF-7 and found that these synthesised compounds possess significant anticancer activity. Further, the compounds 5a and 5e were identified as promising leads due to their better activity across all cell lines than that of the standard drug etoposide. Molecular docking studies of 5a & 5e with DNA Topoisomerase-II were revealed that the free energy calculations of active compounds were in good agreement with observed IC50 values.
- Nerella, Srinivas,Kankala, Shravankumar,Gavaji, Brahmeshwari
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supporting information
p. 9 - 16
(2019/06/27)
-
- Synthesis and antimicrobial studies of novel n-glycosyl hydrazino carbothioamide
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In view of applications of N-glycosylated compounds in medicinal chemistry and in many other ways, herein the synthesis of novel N-glycosyl hydrazino carbothioamides is reported. New N-glycosyl hydrazino carbothioamides were synthesized by the condensation of per-O-acetyl glycosyl isothiocyanate with different aromatic hydrazides. The newly synthesized compounds were characterized by using the IR, 1H NMR and mass spectral studies. Antimicrobial evaluation of the synthesized N-glycosyl hydrazino carbothioamide was also examined. Antimicrobial activities of the synthesized compound were evaluated against bacteria E. coli, P. aeruginosa, S. aureus, S. pyogenus and fungi C. albicans, A. niger and A. clavatus. All the N-glycosyl hydrazino carbothioamides exhibit promising antimicrobial activity.
- Nayak, Riddhi A.,Mangte, Anvita D.
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p. 127 - 131
(2021/01/06)
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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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- CHARGE VARIANT LINKERS
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The present disclosure provides, inter alia, ADCs with charge variant chemical linkers useful in treating various diseases such as cancer and autoimmune disorders.
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Page/Page column 219
(2021/10/15)
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- GLYCOSIDE COMPOUND AND PREPARATION METHOD THEREFOR, COMPOSITION, APPLICATION, AND INTERMEDIATE
-
The present invention discloses a glycoside compound represented by Formula III, and a preparation method, a composition, use and an intermediate thereof. The glycoside compound provided in the present invention has simple preparation method, can significantly increase the expression of VEGF-A mRNA, and is effective in promoting the angiogenesis. This provides a reliable guarantee for the development of drugs with pro-angiogenic activity for treating cerebral infarction cerebral stroke, myocardial infarction, and ischemic microcirculatory disturbance of lower limbs.
- -
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- Synthesis of photolabile group protected anomeric acetals and its application in carbohydrate synthesis with the assistance of continuous flow photo-reactor
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Selective deprotection of photolabile anomeric 2-nitrobenzyl acetals was achieved using continuous flow photo-reactor (UV radiation at 355 nm) in methanol-water. Various protecting groups such as acetyl, benzyl, benzoyl, benzylidine, TBS, etc. were found to be highly stable during the photolysis.
- Tiwari, Varsha,Badavath, Vishnu Nayak,Singh, Adesh Kumar,Kandasamy, Jeyakumar
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p. 227 - 236
(2020/03/18)
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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 0299; 0304-0306
(2020/03/12)
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- Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II
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A series of new carbohydrate-based sulphonamide derivatives were designed, synthesised by employing the so-call ‘sugar-tail’ approach. The compounds were evaluated in vitro against a panel of CAs. Compared to their parent compound p-sulfamoylbenzoic acid, these compounds showed nearly 100-fold improvement in their binding affinities against hCA II in vitro. All of compounds showed great water solubility and the pH value of their water solutions of compounds is 7.0. Such properties are advantageous to make them much less irritating to the eye when applied topical glaucomatous drugs, compared to the relatively highly acidic dorzolamide preparations (pH 5.5). Notably, compounds 7d, 7 g, 7 h demonstrated to topically lower intraocular pressure (IOP) in glaucomatous animals better than brinzolamide when applied as a 1% solution directly into the eye. Low cytotoxicity on human cornea epithelial cell was observed in the tested concentrations by the MTT assay.
- Fan, Zhanfang,Guo, Chun,Hou, Zhuang,Li, Chuanchao,Lin, Bin,Liu, Yang,Liu, Yichuang,Wang, Yitong,Zhang, Miao
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p. 383 - 390
(2019/12/30)
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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.
- -
-
Paragraph 0012-0014
(2020/05/14)
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- The synthesis of rare earth metal-doped upconversion nanoparticles coated with d-glucose or 2-deoxy-d-glucose and their evaluation for diagnosis and therapy in cancer
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Rare earth metal-doped upconversion nanoparticles (UCNPs) are emerging as a new class of biomedical imaging materials due to their higher energy anti-Stokes shift, high optical penetration depth and long term repetitive imaging. In the present study, upconversion nanoparticles based on NaYF4 doped with thulium (Tm) and ytterbium (Yb) were prepared via a thermolysis method using oleic acid as a capping agent and 1-octadecene as a solvent. The X-ray diffraction pattern of the synthesized nanoparticles was found to match the standard hexagonal phase. The nanoparticles were coated with silica using tetraethyl orthosilicate (TEOS) and in order to avoid agglomeration, IGEPAL CO-520 was used as the surfactant. The coatings of SiO2 over NaYF4 were confirmed by the TEM image and XRD pattern. NaYF4@SiO2 was further functionalized by the addition of (3-aminopropyl)trimethoxysilane (APTMS) followed by either d-glucose or 2-deoxy-d-glucose (2-DG). UCNPs-d-glucose and UNCPs-2DG were examined for cell viability (MCF-7 cells) by MTT assay. The cellular uptake of UCNPs in MCF-7 cells was seen in terms of emission of a blue light. Furthermore, the uptake rate of UCNPs coated with 2-deoxy-d-glucose was found to be much faster than that of UCNPs alone under d-glucose starved conditions. The functionalization of UCNPs with 2-deoxy-d-glucose (2-DG) not only increased the uptake of nanoparticles, but also blocked the glycolysis pathway resulting in the inhibition of tumor growth as 2-deoxy-d-glucose (2-DG) is mimicking the d-glucose. The results are indicative that these upconversion nanoparticles may find applications in bio-imaging, removal of tumor by precision surgery, therapy and targeted drug delivery. This journal is
- Sharma, K. Shitaljit,Thoh, Maikho,Dubey, Akhil K.,Phadnis, Prasad P.,Sharma, Deepak,Sandur, Santosh K.,Vatsa, Rajesh K.
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supporting information
p. 13834 - 13842
(2020/09/07)
-
- Addressing the Structural Complexity of Fluorinated Glucose Analogues: Insight into Lipophilicities and Solvation Effects
-
In this work, we synthesized all mono-, di-, and trifluorinated glucopyranose analogues at positions C-2, C-3, C-4, and C-6. This systematic investigation allowed us to perform direct comparison of 19F resonances of fluorinated glucose analogues and also to determine their lipophilicities. Compounds with a fluorine atom at C-6 are usually the most hydrophilic, whereas those with vicinal polyfluorinated motifs are the most lipophilic. Finally, the solvation energies of fluorinated glucose analogues were assessed for the first time by using density functional theory. This method allowed the log P prediction of fluoroglucose analogues, which was comparable to the C log P values obtained from various web-based programs.
- St-Gelais, Jacob,C?té, émilie,Lainé, Danny,Johnson, Paul A.,Giguère, Denis
-
supporting information
p. 13499 - 13506
(2020/10/02)
-
- An Efficient Strategy for the Chemo-Enzymatic Synthesis of Bufalin Glycosides with Improved Water Solubility and Inhibition against Na+, K+-ATPase
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In this study, bufalin was glycosylated by an efficient chemo-enzymatic strategy. Firstly, 2-chloro-4-nitrophenyl-1-O-β-D-glucoside (sugar donors) was obtained by chemical synthesis. Then, the glycosylation of the bufalin was achieved with the synthesized sugar donor under the catalysis of two glycosyltransferases (Loki and ASP). Finally, two glycosides, i. e., bufalin-3-O-β-D-glucopyranoside and bufalin-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside)], were obtained by preparative HPLC. Compared to our previously reported sole chemical (total yield 10 % in four steps) or enzymatic methods (30 %), our combined chemo-enzymatic strategy in this article greatly improves the yields of monoglycoside (68 %) and diglycoside (21 %) and decreased the experimental cost (90 %). Furthermore, we tested the water solubility of these glycosides and found that the water solubilities of the two glycosides were 13.1 and 53.7 times of bufalin, respectively. In addition, the inhibitory activity of these glycosides against Na+, K+-ATPase were evaluated. The mono-glycosylated compound showed more potent activity than bufalin, while the diglycosylated compound was less potent.
- Liu, Yan,Xu, Wei,Huang, Zhao-He,Guo, Jun,Jiang, Ren-Wang
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-
- COMPOUNDS COMPRISING CLEAVABLE LINKER AND USES THEREOF
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Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a -S(=0)(=N-)- functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.
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Page/Page column 141
(2020/09/03)
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- Synthetic methodology towards allylic: Trans-cyclooctene-ethers enables modification of carbohydrates: Bioorthogonal manipulation of the lac repressor
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The inverse electron-demand Diels-Alder (IEDDA) pyridazine elimination is one of the key bioorthogonal bond-breaking reactions. In this reaction trans-cyclooctene (TCO) serves as a tetrazine responsive caging moiety for amines, carboxylic acids and alcohols. One issue to date has been the lack of synthetic methods towards TCO ethers from functionalized (aliphatic) alcohols, thereby restricting bioorthogonal utilization. Two novel reagents were developed to enable controlled formation of cis-cyclooctene (CCO) ethers, followed by optimized photochemical isomerization to obtain TCO ethers. The method was exemplified by the controlled bioorthogonal activation of the lac operon system in E. coli using a TCO-ether-modified carbohydrate inducer. This journal is
- Araman, Can,De Geus, Mark A. R.,Groenewold, G. J. Mirjam,Maurits, Elmer,Van Kasteren, Sander I.
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p. 10175 - 10179
(2020/10/13)
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- Synthesis of one new sugar imine molecule
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In this research, the molecule N'-((E)-5-methoxy-2-((1-((2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)-4,5-dihydro-1H-1,2,3-triazol-4-yl)methoxy) benzylidene)-4methyl-1,2,3-thiadiazole-5-carbohydrazide were synthesized and characterized by several conventional analysis methods. Its physical properties and thermal stability was studied. The synthesis was conducted based on D-glucose using concept of click chemistry reaction mechanism. Some of the reaction was conducted using microwave irradiation. The synthesis steps initiated by adding propargyl bromide to 2-hydroxy-5-methoxy benzaldehyde under vigorous measure of moister isolated environment to produce propargyl ether(5-methoxy-2-(prop-2-yn-1-yloxy)benzaldehyde) 3 in which has terminal triple bond. In parallel a glycocyl azide was prepared by applying glycocyl acetate (acetate for protection) via bromination and then substituted by treatment with sodium azide to produce glycocyl azide in which actively reacted with terminated triple bond by click reaction in the present of Cu(II) catalyst. The coupling reaction of terminal alkyle group in compound 3 with azide group of (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-azidotetrahydro-2H-pyran-3,4,5-triyl triacetate) has given high yield of triazole. The produced triazole molecule is triazole(2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-((2-formyl-4-methoxy)methyl)-1H-1,2,3-triazole-1-yl)tetrahydro-2H-pyran-3,4,5,-triyacetate) 7 undergoes further reaction to substitute carbonyl of the aromatic with hydrazide by applying 4-methyl-1,2,3-thiadiazole-5-carbohydrazide reagent. The glycocyl acetate was de-esterifide by sodium methoxide to remove the acetate protection. The structure of all these synthesized molecules was confirmed by FTIR, H1NMR, C13 NMR.
- Mohammed, Majed Jari,Kadhum, Abdul Amir H.,Mohammed, Adnan Ibrahim,Abbood Al-Rekabi, Sameer H.
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p. 103 - 108
(2020/02/13)
-
- Glycosides and Glycoconjugates of the Diterpenoid Isosteviol with a 1,2,3-Triazolyl Moiety: Synthesis and Cytotoxicity Evaluation
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Several glycoconjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with a 1,2,3-triazolyl moiety were synthesized, and their cytotoxicity was evaluated against some human cancer and normal cell lines. Most of the synthesized compounds demonstrated weak inhibitory activities against the M-HeLa and MCF-7 human cancer cell lines. Three lead compounds, 54, 56 and 57, exhibited high selective cytotoxic activity against M-HeLa cells (IC50 = 1.7-1.9 μM) that corresponded to the activity of the anticancer drug doxorubicin (IC50 = 3.0 μM). Moreover, the lead compounds were not cytotoxic with respect to a Chang liver human normal cell line (IC50 > 100 μM), whereas doxorubicin was cytotoxic to this cell line (IC50 = 3.0 μM). It was found that cytotoxic activity of the lead compounds is due to induction of apoptosis proceeding along the mitochondrial pathway. The present findings suggest that 1,2,3-triazolyl-ring-containing glycoconjugates of isosteviol are a promising scaffold for the design of novel anticancer agents.
- Andreeva, Olga V.,Garifullin, Bulat F.,Sharipova, Radmila R.,Strobykina, Irina Yu.,Sapunova, Anastasiya S.,Voloshina, Alexandra D.,Belenok, Mayya G.,Dobrynin, Alexey B.,Khabibulina, Leysan R.,Kataev, Vladimir E.
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p. 2367 - 2380
(2020/08/28)
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- Oleanolic acid C-3-site sugar conjugate, preparation method and anti-influenza virus application thereof
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The invention provides an oleanolic acid-C-3-site sugar conjugate with a structure shown as a formula (I) or pharmaceutically acceptable salt thereof and a preparation method thereof. The oleanolic acid-C3-site sugar conjugate has an obvious inhibiting effect on influenza viruses and can be used for preparing a medicine for preventing or treating influenza and a drug for preventing or inhibiting the entry of influenza viruses into cells.
- -
-
Paragraph 0035-0036; 0039
(2020/12/05)
-
- 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
-
supporting information
p. 587 - 591
(2019/01/04)
-
- 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.
- -
-
Paragraph 0087-0088; 0094-0098
(2019/10/29)
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- Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity
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The development of entry inhibitors is an emerging approach to the inhibition of influenza virus. In our previous research, oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor. Herein, as a further study, we report the preparation of a series of OA-saccharide conjugates via the CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 11b, an OA-glucose conjugate, showed a significantly increased anti-influenza activity with an IC50 of 5.47 μM, and no obvious cytotoxic effect on MDCK cells was observed at 100 μM. Hemagglutination inhibition assay and docking experiment indicated that 11b might interfere with influenza virus infection by acting on HA protein. Broad-spectrum anti-influenza experiments showed 11b to be robustly potent against 5 different strains, including influenza A and B viruses, with IC50 values at the low-micromole level. Overall, this finding further extends the utility of OA-saccharide conjugates in anti-influenza virus drug design.
- Su, Yangqing,Meng, Lingkuan,Sun, Jiaqi,Li, Weijia,Shao, Liang,Chen, Kexuan,Zhou, Demin,Yang, Fan,Yu, Fei
-
-
- Sugar molecules coupled diketopyrrolo pyrrole compound in the application in the preparation of yellow pigment, yellow pigment and a yellow pigment preparation method
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The invention relates to application of a sugar molecule coupling diketopyrrolopyrrole compound shown as a general formula (I) to preparation of a yellow pigment, wherein R1 is H, Br, Cl, F, CN, C1-8straight chain or branch-chain alkyls, substituted or unsubstituted aromatic alkyls, C1-8 straight chain or branch-chain alkyls, and C1-8 single-substituted or double-substituted amino groups; A is mono-glycosyl, di-glycosyl or tri-glycosyl; B is H or the mono-glycosyl, di-glycosyl or tri-glycosyl identical to the A. The invention also relates to the yellow pigment and a preparation method of theyellow pigment. The formula I is shown in the description.
- -
-
Paragraph 0110-0111; 0114-0115
(2019/05/06)
-
- NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
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The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.
- -
-
Paragraph 0642-0643
(2019/12/24)
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- Development of a two-photon fluorescent probe for the selective detection of β-galactosidase in living cells and tissues
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The development of two-photon bio-imaging probes for trapping specific enzyme activities in overexpressed tissue is very practical and significant. In this work, we developed a two-photon fluorescent β-gal probe G-GAL, which was made with GCTPOC as the fluorescence reporter and a β-galactosidase cleavable crew as the enzyme activity initiator. The purpose of designing this probe was to detect β-galactosidase in living cells and tissues. The probe G-GAL has the advantage of rapid response, great fluorescence enhancement and superior specificity. Furthermore, the probe has excellent tissue penetration.
- Li, Zihong,Ren, Mingguang,Wang, Li,Dai, Lixuan,Lin, Weiying
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supporting information
p. 3431 - 3437
(2019/06/08)
-
- Acetyl-protected galactose analogue and preparation method thereof
-
The invention discloses an acetyl-protected galactose analogue and a preparation method thereof. The acetyl-protected galactose analogue has a structural formula as shown in the specification. The acetyl-protected galactose analogue is synthesized by a click chemistry method. The preparation method is simple and the yield is high; and the galactose analogue can be used as a precursor for preparinga positron imaging agent targeted to an ASGPR (Asialoglycoprotein receptor).
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-
Paragraph 0059; 0061; 0065
(2019/02/04)
-
- Method for detecting β - galactosidase fluorescent probe and the preparation method and application (by machine translation)
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The invention provides a method for detecting β - galactosidase fluorescent probe and the preparation method and application. The detection β - galactosidase fluorescent probe is of the structural formula: . The above β - galactosidase probe can be applied to the cell in the content of β - galactosidase sensing detection. As the display solution and in cells in the presence of β - galactosidase specific indicator. The invention is a simple, fast, sensitive β - galactosidase specific detection reagent, in biological molecular detection field and has broad application prospects. (by machine translation)
- -
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Paragraph 0019
(2019/01/23)
-
- ANTI-EGFR ANTIBODY DRUG CONJUGATES
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The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.
- -
-
Paragraph 1005
(2019/06/07)
-
- Formation of five-membered carbocycles from D-glucose: A Concise Synthesis of 4-Hydroxy-2-(hydroxymethyl)cyclopentenone
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A concise synthesis of 4-hydroxy-2-(hydroxymethyl)cyclo-pentenone (1) has been accomplished from D-glucose by a three-step sequence that features a catalyst-free hydrothermal reaction of D-glucal, which is readily obtained from D-glucose. Optimization of the reaction conditions for synthesizing 1 was performed by changing the temperature and reaction time. The treatment of D-glucal under the optimal conditions, i.e., at 120 °C for 24 h, provided 1 in the highest isolated yield of 61%. 1 would become a versatile intermediate for the synthesis of various fine chemicals having a cyclopentenone structure from cellulosic biomass.
- Koseki, Yoshitaka,Watanabe, Toshihiro,Kamishima, Takaaki,Kwon, Eunsang,Kasai, Hitoshi
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p. 1324 - 1328
(2019/09/18)
-
- Synthesis of C3-Neoglycosides of digoxigenin and their anticancer activities
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Cardiac glycosides exhibit significant anticancer effects and the glycosyl substitution at C3 position of digoxigenin is pivotal for their biological activity. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and explore more potent anticancer agents, a series of C3-O-neoglycosides and C3-MeON-neoglycosides of digoxigenin were synthesized by the Koenigs-Knorr and neoglycosylation method, respectively. In addition, digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by sodium periodate (NaIO4) oxidation and 6-aminocaproic acid hydrolysis. The SAR analysis revealed that C3-O-neoglycosides of digoxigenin exhibited stronger cytotoxicity and induction of Nur77 expression of tumor cells than C3-MeON-neoglycosides. Also, 3β-O-glycosides exhibited stronger anticancer effects than 3α-O-glycosides. Among them, 3β-O-(β-L-fucopyranosyl)-digoxigenin (3i) showed the highest activity on induction of Nur77 expression and translocation from the nucleus to cytoplasm, leading to cancer cell apoptosis.
- Li, Xiao-san,Ren, Yi-chang,Bao, Yu-zhou,Liu, Jie,Zhang, Xiao-kun,Zhang, You-wei,Sun, Xue-Long,Yao, Xin-sheng,Tang, Jin-Shan
-
supporting information
p. 252 - 262
(2018/01/12)
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- A five-component one-pot synthesis of phosphatidylinositol pentamannoside (PIM5)
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A practical and efficient synthesis of phosphatidylinositol pentamannoside (PIM5) was achieved based on a five-component one-pot sequential glycosylation protocol with exclusive regio- and stereo-selectivity. Two regioselective sequential glycosylations on inositol and p-tolyl thioglycosides as the sole type of building blocks made this protocol to avoid the tedious protective group manipulations. This synthetic strategy provides access to other important glycolipids with similar structures.
- Wang, Dong,Xiong, De-Cai,Ye, Xin-Shan
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p. 1340 - 1342
(2018/01/08)
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- Total Synthesis of a Densely Functionalized Plesiomonas shigelloides Serotype 51 Aminoglycoside Trisaccharide Antigen
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Plesiomonas shigelloides, a pathogen responsible for frequent outbreaks of severe travelers' diarrhea, causes grave extraintestinal infections. Sepsis and meningitis due to P. shigelloides are associated with a high mortality rate as antibiotic resistance increases and vaccines are not available. Carbohydrate antigens expressed by pathogens are often structurally unique and are targets for developing vaccines and diagnostics. Here, we report a total synthesis of the highly functionalized trisaccharide repeating unit 2 from P. shigelloides serotype 51 from three monosaccharides. A judicious choice of building blocks and reaction conditions allowed for the four amino groups adorning the sugar rings to be installed with two N-acetyl (Ac) groups, rare acetamidino (Am), and d-3-hydroxybutyryl (Hb) groups. The strategy for the differentiation of amino groups in trisaccharide 2 will serve well for the syntheses of other complex glycans.
- Qin, Chunjun,Schumann, Benjamin,Zou, Xiaopeng,Pereira, Claney L.,Tian, Guangzong,Hu, Jing,Seeberger, Peter H.,Yin, Jian
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supporting information
p. 3120 - 3127
(2018/03/08)
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- Application of sugar molecule coupled diketone pyrrolo-pyrrole compound in preparing red pigment for plastic, red pigment for plastic and preparation method
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The invention relates to application of sugar molecule coupled diketone pyrrolo-pyrrole compound shown as a general formula (I) in preparing easy-to-disperse red pigment for plastic. R1 is H, Br, Cl,F, CN, C1-8 linear-chain or branched-chain alkyl, substituted or unsubstituted aromatic alkyl, C1-8 linear-chain or branched-chain alkoxy, C1-8 mono-substituted or bis-substituted amino, A is mono-glycosyl, bis-glycosyl or tri-glycosyl, and B is H or mono-glycosyl, bis-glycosyl or tri-glycosyl same as A. The invention further relates to the easy-to-disperse red pigment for plastic and a preparation method thereof.
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Paragraph 0089; 0093; 0094
(2018/03/26)
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- Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones
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A series of arylnaphthalene lignan lactones based on the structure of the phyllanthusmins, a class of potent natural products possessing diphyllin as the aglycone, has been synthesized and screened for activity against multiple cancer cell lines. SAR exploration was performed on both the carbohydrate and lactone moieties of this structural class. These studies have revealed the importance of functionalization of the carbohydrate hydroxy groups with both acetylated and methylated analogues showing increased potency relative to those with unsubstituted sugar moieties. In addition, the requirement for the presence and position of the C-ring lactone has been demonstrated through reduction and selective re-oxidation of the lactone ring. The most potent compound in this study displayed an IC50 value of 18 nM in an HT-29 assay with several others ranging from 50 to 200 nM. In an effort to elucidate their potential mechanism(s) of action, the DNA topoisomerase IIa inhibitory activity of the most potent compounds was examined based on previous reports of structurally similar compounds, but does not appear to contribute significantly to their antiproliferative effects.
- Woodard, John L.,Huntsman, Andrew C.,Patel, Pratiq A.,Chai, Hee-Byung,Kanagasabai, Ragu,Karmahapatra, Soumendrakrishna,Young, Alexandria N.,Ren, Yulin,Cole, Malcolm S.,Herrera, Denisse,Yalowich, Jack C.,Kinghorn, A. Douglas,Burdette, Joanna E.,Fuchs, James R.
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p. 2354 - 2364
(2018/04/16)
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- Synthesis of some monosaccharide-related ester derivatives as insecticidal and acaricidal agents
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To develop natural-product-based pesticidal agents, a series of monosaccharide-related ester derivatives (17a–q and 18a–f), glucose (xylose)-piperic acid/piperic acid-like conjugates, were synthesized. Three-dimensional structures of compounds 17b, 17g, 17h, and 17n were unambiguously determined by single-crystal X-ray diffraction. Especially compounds 18e and 18f exhibited the most potent insecticidal and acaricidal activities against Mythimna separata and Tetranychus cinnabarinus. Their structure-activity relationships were also discussed.
- Huang, Xiaobo,Zhang, Bingchuan,Xu, Hui
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p. 4336 - 4340
(2017/09/12)
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- Ratiometric electrochemical detection of β-galactosidase
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A novel ferrocene-based substrate for the ratiometric electrochemical detection of β-galactosidase was designed and synthesised. It was demonstrated to be an excellent electrochemical substrate for β-Gal detection with sensitivity as low as 0.1 U mL-1.
- Spring, Sam A.,Goggins, Sean,Frost, Christopher G.
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supporting information
p. 7122 - 7126
(2017/09/07)
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- ANTI-CD98 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
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The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
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Page/Page column 318
(2018/01/15)
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- Synthesis of Glycosylated Chrysin Derivatives Via Ester Linkers
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A series of glycosylated chrysin derivatives have been synthesized in good yields with simple procedures and mild reaction conditions. Six different kinds of sugar moieties were introduced through each ester linker.
- Fei, Gaishun,Fan, Xiaofei,Ma, Huiping,Fan, Pengchang,Jia, Zhengping,Jing, Linlin
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p. 602 - 610
(2016/08/31)
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- Bisindolyl maleimide derivative and preparation method and application thereof
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The invention provides a bisindolyl maleimide derivative and a preparation method and application thereof. The bisindolyl maleimide derivative has an excellent alpha-glucosidase inhibition effect and can be used for preventing and treating diabetes.
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Paragraph 0752
(2017/01/02)
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- A bromo tetra acetyl glucose synthesis method
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The invention relates to a synthetic method of bromotetracetylglucose. The synthetic method is characterized in that triethylamine is regarded as an acetylation catalyst, an acetic acid solution of hydrobromic acid is regarded as a brominating reagent, and the bromotetracetylglucose is prepared by a two-step method. The method is safe to operate, low in cost, and very suitable for large-scale production.
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Paragraph 0030; 0031; 0032
(2017/02/17)
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- Efficient Synthesis of Glycosylated Matijin-Su Derivatives via Ultrasonic Irradiation
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Matijin-Su (1) is a phenylalanine dipeptide compound with anti-hepatitis B virus (HBV) activity. Previous reports suggest that the synthesis of glycosylated Matijin-Su derivatives needs at least 10 steps. To simplify the synthetic procedure, we have developed a shorter and more efficient method for the preparation via ultrasound irradiation. Two galactopyranosylated (2) and two glucopyranosylated (3) derivatives were synthesized in 6 or 7 steps. The overall yields for the total synthesis of galactopyranosylated derivatives were markedly increased to 39% (2a) or 22% (2b). And the yields for glucopyranosylated derivatives also reached 29% (3a) or 16% (3b).
- Liang, Guangping,Hu, Zhanxing,Yuan, Jie,Liang, Guangyi,Xu, Bixue
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p. 1353 - 1359
(2016/12/27)
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- A 4-methyl umbrella-type keto -β-D method for preparing-galactopyranoside
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The invention discloses a preparation method of 4-methyl umbrella-shaped keto-beta-D-pyran galactoside. The method comprises the following steps: step 1, preparing 4-methyl umbrella-shaped ketone; step 2, preparing tetra acetyl-Alpha-D-pyran galactoside; step 3, preparing 4-methyl umbrella-shaped keto-2,3,4,6-tetra acetyl-beta-D-pyran galactoside; and step 4, preparing the 4-methyl umbrella-shaped keto-beta-D-pyran galactoside. The method is moderate in reaction condition, namely, the reactions are carried out at a room temperature; heavy metallic salts are not required, so that the environmental friendliness is realized; the yield is high, namely, the one-step yield of glycosylations can reach 73.1% and the total yield of the glycosylations can rach 32.9%. The microbiology experiment proves that the effects of the 4-methyl umbrella-shaped keto-beta-D-pyran galactoside are equal to the effects of an imported substrate, so that the 4-methyl umbrella-shaped keto-beta-D-pyran galactoside can be used for replacing an imported product.
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Paragraph 0046; 0048
(2017/03/14)
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- ANTIBODY DRUG CONJUGATES WITH CELL PERMEABLE BCL-XL INHIBITORS
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Small molecule Bcl-xL inhibitors and Antibody Drug Conjugates (ADCs) comprising small molecule Bcl-xL inhibitors are disclosed herein. The Bcl-xL inhibitors and ADCs of the disclosure are useful for, among other things, inhibiting anti-apoptotic Bcl xL proteins as a therapeutic approach towards the treatment of diseases that involve a dysregulated apoptosis pathway.
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Paragraph 000336; 000526
(2016/07/05)
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- NEW HYDROXYACID DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R8, R14, A and n are as defined in the description. Medicaments.
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Page/Page column 47; 48
(2017/01/09)
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- Bisindolylmaleimide derivative, and preparation method and use thereof
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The invention provides a bisindolylmaleimide derivative, and a preparation method and a use thereof. The bisindolylmaleimide derivative has a good tumor treatment effect, especially has a good treatment effect on some drug-resistant tumors, and can realize accurate treatment of the drug-resistant tumors.
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Page/Page column 0754; 0755
(2017/04/03)
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- Curcumin Monoglucoside Shows Improved Bioavailability and Mitigates Rotenone Induced Neurotoxicity in Cell and Drosophila Models of Parkinson’s Disease
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Curcumin (CUR), a dietary polyphenol has diverse pharmacologic effects, but is limited by poor bioavailability. This is probably due to decreased solubility, cellular uptake and stability. In order to enhance its solubility and bioavailability, we synthesized the CUR bioconjugate curcumin monoglucoside (CMG) and tested its bioavailability, neuroprotective and anti-apoptotic propensity against rotenone (ROT) induced toxicity in N27 dopaminergic neuronal cells and Drosophila models. Our results elucidate that CMG showed improved bioavailability than CUR in N27 cells. Pre-treatment with CMG protected against ROT neurotoxicity and exerted antioxidant effects by replenishing cellular glutathione levels and significantly decreasing reactive species. CMG pre-treatment also restored mitochondrial complex I and IV activities inhibited by ROT. ROT-induced nuclear damage was also restored by CMG as confirmed by comet assay. CMG induced anti-apoptotic effects was substantiated by decreased phosporylation of JNK3 and c-jun, which in turn decreased the cleavage of pro-caspase 3. Q-PCR analysis of redox genes showed up-regulation of NOS2 and down-regulation of NQO1 upon ROT exposure and this was attenuated by CMG pre-treatment. Studies in the Drosophila ROT model revealed that, CMG administration showed better survival rate and locomotor activity, improved antioxidant activity and dopamine content than ROT treated group and was comparable with the CUR group. Based on these data, we surmise that CMG has improved bioavailability and offered neuroprotection comparable with CUR, against ROT-induced toxicity both in dopaminergic neuronal cell line and Drosophila models, with therapeutic implications for PD.
- Pandareesh,Shrivash,Naveen Kumar,Misra,Srinivas Bharath
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p. 3113 - 3128
(2016/11/11)
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- Stereocontrolled Synthesis of Phenolic α-d-Glycopyranosides
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Adopting the ‘remote activation concept’ toward stereocontrolled glycoside synthesis with minimal use of protection groups, a general synthesis of phenolic 1,2-cis glycopyranosides is reported, as exemplified by aryl α-d-galacto-, α-d-gluco- and 2-azido α-d-glucopyranosides among others using glycosyl donors bearing an anomeric (3-bromo-2-pyridyloxy) group and catalyzed by methyl triflate.
- St-Pierre, Gabrielle,Dafik, Laila,Klegraf, Ellen,Hanessian, Stephen
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p. 3575 - 3588
(2016/10/17)
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- Directed interactions of block copolypept(o) ides with mannose-binding receptors: Peptomicelles targeted to cells of the innate immune system
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Core-shell structures based on polypept(o)ides combine stealth-like properties of the corona material polysarcosine with adjustable functionalities of the polypeptidic core. Mannose-bearing block copolypept(o)ides (PSar-block-PGlu(OBn)) have been synthesized using 11-amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside as initiator in the sequential ring-opening polymerization of α-amino acid N-carboxyanhydrides. These amphiphilic block copolypept(o)ides self-assemble into multivalent PeptoMicelles and bind to mannose-binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.
- Heller, Philipp,Mohr, Nicole,Birke, Alexander,Weber, Benjamin,Reske-Kunz, Angelika,Bros, Matthias,Barz, Matthias
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- WATER-SOLUBLE PHOTOCHROMIC MOLECULE
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A diarylethene compound having high water-solubility is provided, and the compound is a diarylethene compound of formula (I) wherein, Sg is a monovalent sugar-type residue consisting of a sugar-type compound (in which some of hydroxyl groups may be protected) selected from a group consisting of a six-membered ring sugar, a five-membered ring sugar, cyclitol and oligosaccharides containing a six-membered ring sugar, a five-membered ring sugar, or cyclitol and excluding an hydroxyl group; U is -(CH2)n-, -CH2-U'-, or -C(=O)- (wherein, n is an integer of 1 to 5, U' is a C1-C10 alkyl group binding to Ar); and Ar is a group represented by formula (A1) or (A2); wherein, X is S, SO2, NR3 (R3 is a C1-C3 alkyl group) or O, R is C1-C4 alkyl group, R1 and R2 are independently a C1-C3 alkyl group, a is 0 or 1, b is an integer of 0-3, and * represents a bond with U); Y is a hydrogen atom or a halogen atom; m is an integer of 5-7.
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Paragraph 0066
(2015/09/22)
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