53784-33-1Relevant articles and documents
Anomeric effect of the nitrogen atom in the isocyano and urea groups
Ichikawa, Yoshiyasu,Watanabe, Hitomi,Kotsuki, Hiyoshizo,Nakano, Keiji
, p. 6331 - 6337 (2010)
The anomeric effect associated with the nitrogen atom in the isocyano group was investigated by using 1H NMR spectroscopic analysis of an anomeric pair of xylopyranosyl isocyanides 8 and 7. We found that β-anomer 7 prefers to exist in the 1C4 conformation in which the nitrogen atom in the isocyano group adopts an axial orientation. This observation, coupled with the results of X-ray crystallographic analysis establishes that the nitrogen atom in the isocyano group displays the anomeric effect. Furthermore, xylopyranosyl isocyanides 8 and 7 were transformed into the corresponding xylopyranosyl ureas 10 and 11. In the case of the urea group, a normal sterically determined preference is observed in which the bulky urea substituents at the pyranose anomeric position occupy the equatorial position. Copyright
Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity
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
, (2021/11/23)
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.
Synthesis of podophyllotoxin-glycosyl triazoles via click protocol mediated by silver (I)-N-heterocyclic carbenes and their anticancer evaluation as topoisomerase-II inhibitors
Nerella, Srinivas,Kankala, Shravankumar,Gavaji, Brahmeshwari
, p. 9 - 16 (2019/06/27)
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.
Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II
Fan, Zhanfang,Guo, Chun,Hou, Zhuang,Li, Chuanchao,Lin, Bin,Liu, Yang,Liu, Yichuang,Wang, Yitong,Zhang, Miao
, p. 383 - 390 (2019/12/30)
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.
Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity
Su, Yangqing,Meng, Lingkuan,Sun, Jiaqi,Li, Weijia,Shao, Liang,Chen, Kexuan,Zhou, Demin,Yang, Fan,Yu, Fei
, (2019/08/20)
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.
Synthesis of biurets: Via TMSNCO addition to 1-aminosugars: Application in the de novo synthesis of dC oxidation products
Tsoulougian, Veronika,Psykarakis, Emmanuel E.,Gimisis, Thanasis
, p. 973 - 981 (2019/02/01)
The reaction between 1-aminosugars and trimethylisocyanate (TMSNCO) was optimised as a one-step synthetic strategy for the synthesis of sugar biurets. This protocol was successfully applied to a number of 1-aminosugars, which exclusively provided the corresponding biurets in 67-99% yields. The new methodology was applied in the de novo synthesis of N1-(2-deoxy-α/β-d-erythro-pentofuranosyl)biuret (dfBU) and N1-(2-deoxy-α/β-d-erythro-pentopyranosyl)biuret (dpBU), two known DNA lesions arising from the hydroxyl radical induced decomposition of 2′-deoxycytidine (dCyd).
AuBr3-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars
Rajput, Jayashree,Hotha, Srinivas,Vangala, Madhuri
, p. 682 - 687 (2018/03/30)
Herein we report, for the first time, the successful anomeric azidation of per-O-acetylated and per-O-benzoylated sugars by catalytic amounts of oxophilic AuBr3 in good to excellent yields. The method is applicable to a wide range of easily accessible per-Oacetylated and per-O-benzoylated sugars. While reaction with per-O-acetylated and per-O-benzoylated monosaccharides was complete within 1-3 h at room temperature, the per-O-benzoylated disaccharides needed 2-3 h of heating at 55°C.
Aglycone Ebselen and β- D -Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen β- D -Xyloside-Induced Cytotoxicity
Tang, Yang,Zhang, Siqi,Chang, Yajing,Fan, Dacheng,Agostini, Ariane De,Zhang, Lijuan,Jiang, Tao
, p. 2937 - 2948 (2018/04/23)
Most β-d-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to d-xylose, d-glucose, d-galactose, and d-lactose (8A-D), only Ebselen β-d-xyloside (8A) showed significant cytotoxicity in human cancer cells. The following facts indicated that the aglycone Ebselen and β-d-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase cancer cell apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-β-d-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans.
Ruthenium(II)- and copper(I)-catalyzed synthesis of click-xylosides and assessment of their glycosaminoglycan priming activity
Mencio, Caitlin P.,Garud, Dinesh R.,Doi, Yosuke,Bi, Yiling,Vankayalapati, Hariprasad,Koketsu, Mamoru,Kuberan, Balagurunathan
, p. 5027 - 5030 (2017/10/18)
Xylosides are small molecules that serve as primers of glycosaminoglycan biosynthesis. Xyloside mediated modulation of biological functions depends on the extent of priming activity and fine structures of primed GAG chains. In earlier studies, copper (Cu)
Synthetic transformations of higher terpenoids: XXXVI. Synthesis of furanolabdanoid glycoconjugates with a 1,2,3-triazole linker
Kremenko,Kharitonov, Yu. V.,Shul’ts
, p. 35 - 46 (2017/03/16)
Procedures have been developed for the synthesis of 16-[(propargyloxy)methyl]- and 7- and 18-(propargyloxy)labda-8(9),13,14-trienes from phlomisoic acid. Copper-catalyzed cycloaddition of the labdanoid alkynes to azido derivatives of α-D-glucose, D-galactose, D-xylose, and L-arabinose afforded the corresponding N-glycosyl-1,2,3-triazole conjugates.
