Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flavonoids (103 species) were tested for inhibitory activity against mouse liver sialidase using sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate (PNP-NeuAc) as substrate. Isoscutellarein-8-O-glucuronide from the leaf of Scutellaria baicalensis showed most potent activity (IC50, 40 microM), and this flavone appeared to be a non-competitive inhibitor of the enzyme. This flavone inhibited the lysosomal solubilized sialidase against PNP-NeuAc and sialyllactose effectively, but not microsomal enzyme against gangliosides and colominic acid, whereas, negligible or weak inhibitory activities were observed for influenza virus sialidase, beta-galactosidase, alpha-mannosidase, and alpha-glucosidase tested. These results indicate that this flavone may be useful to elucidate the function of the lysosomal solubilized sialidase.
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PMID:Inhibition of mouse liver sialidase by plant flavonoids. 277 64

The alpha-glucosidase inhibitor bromoconduritol inhibits the formation of the N-linked, complex-type oligosaccharides of the glycoproteins from influenza viruses (fowl plague virus, influenza virus PR-8) and from sindbis virus. Viral glycoproteins produced in bromoconduritol-treated chicken-embryo and baby-hamster kidney cells are fully glycosylated, but accumulate N-linked, high-mannose oligosaccharides of the composition Glc1Manx (GlcNAc)2 (x = 7, 8, and 9). Other alpha-glucosidase inhibitors (nojirimycin, deoxynojirimycin, acarbose) were not specific inhibitors of oligosaccharide processing under the conditions used in the present investigation. In bromoconduritol-treated, sindbis virus-infected chicken-embryo and baby-hamster kidney cells, the sindbis glycoproteins are metabolically stable. Specific proteolytic cleavage of the polyprotein precursors to form E2 and E1 occurs in bromoconduritol-treated chicken-embryo cells, but cleavage of PE2 to E2 is prevented in the infected baby-hamster kidney cells. Yet, release of infectious sindbis virus particles is inhibited in both cell types indicating that the formation of complex oligosaccharides is required for a late step in virus formation. The release of virus particles from influenza virus PR-8-infected bromoconduritol-treated chicken-embryo cells is not inhibited, and virus with only high-mannose oligosaccharides is formed. In contrast, when chicken-embryo cells were infected with the influenza virus fowl plague virus, release of infectious particles was inhibited. The fowl plague virus hemagglutinin is cleaved in chicken-embryo cells, in contrast to the hemagglutinin of the PR-8 virus. However, the cleavage products HA1 and HA2 do not reach the cell surface. In addition, or as a consequence, HA1 and HA2 are proteolytically broken down, whereas uncleaved hemagglutinin of PR-8 appeared metabolically stable. These results may explain the decrease in formation of fowl plague virus particles and the lack of effect on PR-8 virus in bromoconduritol-treated cells. This work thus shows different biological roles for oligosaccharide processing.
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PMID:On the role of oligosaccharide trimming in the maturation of Sindbis and influenza virus. 674 24

The alpha-glucosidase inhibitor bromoconduritol (6-bromo-3,4,5-trihydroxycyclohex-1-ene) inhibits trimming of the innermost glucose residue from the Glc3Man9GlcNAc2 precursor of high-mannose and complex oligosaccharides. This inhibition occurs both in intact cells and with a microsomal enzyme preparation. The formation of lipid-linked oligosaccharides was increased in glucosidase-inhibited cells. Inhibition of transfer of high-mannose oligosaccharides to protein was not observed. In bromoconduritol-treated virus-infected cells, trimming of mannose can occur despite incomplete removal of glucose. The glucosylated high-mannose oligosaccharides GlcMan9GlcNAc, GlcMan8GlcNAc, and GlcMan7GlcNAc were released from viral glycoproteins after digestion with Pronase and endo-beta-N-acetylglucosaminidase H. The formation of complex oligosaccharides was concomitantly inhibited. The release of infectious fowl plague virus particles (an influenza virus) was inhibited from bromoconduritol-treated infected chicken-embryo cells.
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PMID:Inhibition of formation of complex oligosaccharides by the glucosidase inhibitor bromoconduritol. 675 22

A number of unusual and rare carbohydrates were tested as potential inhibitors of various glycosidases, as well as inhibitors of N-linked oligosaccharide processing. The best inhibitors of several arylglycosidases and of glucosidase I were L-xylulose and L-fructose. Both of these sugars showed some inhibitory activity towards yeast alpha-glucosidase but were inactive against beta-glucosidase and other arylglycosidases. The inhibition of yeast alpha-glucosidase by L-xylulose was of a competitive nature and required a concentration of 1 x 10(-5) M for 50% inhibition. Both L-xylulose and L-fructose also inhibited the purified soybean glucosidase I, with 50% inhibition occurring at about 1 x 10(-4) M, but showed no inhibitory activity against soybean glucosidase II. When influenza virus-infected MDCK cells were raised in the presence of L-xylulose, there was a dose-dependent inhibition in the formation of complex types of oligosaccharides on the viral glycoproteins consistent with the inhibition of the processing glucosidase I. This inhibition resulted in the occurrence of oligosaccharides on the viral glycoproteins that were characterized as Glc3Man9(GlcNAc)2 structures. L-Fructose also inhibited glycoprotein processing in cell culture, and the inhibition resulted in the formation of similar oligosaccharides to those seen with L-xylulose. However, L-fructose was a poorer inhibitor than L-xylulose and required much higher concentrations for the same degree of inhibition. Neither of these compounds inhibited protein synthesis or the formation of lipid-linked saccharides in culture MDCK cells, even when tested at concentrations of 5 mg/ml (about 30 mM) of culture media.
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PMID:Inhibition of glycoprotein processing by L-fructose and L-xylulose. 902 40

Glycosidases play an important role in a wide range of physiological and pathological conditions, and have become potential targets for the discovery and development of agents useful for the treatment of diseases such as diabetes, cancer, influenza, and even AIDS. In this study, several benzimidazole derivatives were prepared from o-phenylenediamine and aromatic and heteroaromatic carboxaldehydes in very good yields, using PdCl2(CH3CN)2 as the most efficient catalyst. Synthesized compounds were assayed for their activity on yeast and rat intestinal alpha-glucosidase inhibition and cytotoxic activity against colon carcinoma cell line HT-29. Compound 3e exhibited 95.6% and 75.3% inhibition of yeast and rat intestinal alpha-glucosidase enzyme, while showing 74.8% cytotoxic activity against the HT-29 cell line at primary screening concentrations of 2.1 mM for yeast and rat intestinal alpha-glucosidase enzyme and 0.2 mM for cytotoxic activity against the HT-29 cell line, respectively. Compound 3c displayed 76% and 34.4% inhibition of yeast and rat intestinal alpha-glucosidase enzyme, and 80.4% cytotoxic activity against the HT-29 cell line at similar primary screening concentrations. The IC50 value for the most potent intestinal alpha-glucosidase inhibitor compound 3e was found to be 99.4 microM. The IC50 values for the most active cytotoxic compounds 3c and 3e were 82 microM and 98.8 microM, respectively. Both compounds displayed significant antihyperglycemic activity in starch-induced postprandial hyperglycemia in rats. This is the first report assigning yeast and rat intestinal alpha-glucosidase enzyme inhibition, cytotoxic activity against the HT-29 cell line, and antihyperglycemic activity to benzimidazole compounds 3c and 3e.
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PMID:New antihyperglycemic, alpha-glucosidase inhibitory, and cytotoxic derivatives of benzimidazoles. 2003 May 12