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)

The synthesis of new chain-extended sulfonium and selenonium salts of 1,4-anhydro-4-thio-(or 4-seleno)-d-arabinitol, analogues of the naturally occurring glycosidase inhibitor salacinol, is described. Nucleophilic attack at the least hindered carbon atom of 4,6-O-benzylidene-2,5-di-O-p-methoxybenzyl-d-mannitol-1,3-cyclic sulfate by 2,3,5-tri-O-p-methoxybenzyl-1,4-anhydro-4-thio-(or 4-seleno)-d-arabinitol gave the sulfonium and selenonium sulfates, respectively. Subsequent deprotection with trifluoroacetic acid yielded the target compounds. In these analogues, an extended polyhydroxylated aliphatic side chain has been incorporated while maintaining the stereochemistry of C-2' and C-3' of salacinol or blintol. These compounds were designed to probe the premise that they would bind with higher affinity to glucosidases than salacinol because the extra hydroxyl groups in the acyclic chain would make favorable polar contacts within the active site. Both target compounds inhibited recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with Ki values in the low micromolar range. Comparison of these values to those of related compounds synthesized in previous studies has provided a better understanding of structure-activity relationships and the optimal stereochemistry at the different stereogenic centers required of an inhibitor of this enzyme. With respect to chain extension, the configurations at C-2' and C-4' are critical for activity, the configuration at C-3', bearing the sulfate moiety, being unimportant. The desired configuration at C-5' is also specified. However, comparison of the activities of the chain-extended analogues with those of salacinol and blintol indicates that there is no particular advantage of the chain-extension relative to salacinol or blintol. These results are similar to those reported earlier for kotalanol, a 7-carbon-extended derivative, versus salacinol against rat intestinal maltase, sucrase, and isomaltase.
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PMID:New chain-extended analogues of salacinol and blintol and their glycosidase inhibitory activities. Mapping the active-site requirements of human maltase glucoamylase. 1719 97

The synthesis of chain-modified analogues of the naturally-occurring glycosidase inhibitor, salacinol, and its selenium analogue, blintol is described. The modification consists of a frame shift of the sulfate moiety by one carbon atom in the zwitterionic structures as well as an extension of the acyclic chain to five carbons. The target molecules were synthesized by alkylation of 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio (or seleno)-D-arabinitol at the ring heteroatom by 2,3,5-tri-O-p-methoxybenzyl D- or L-xylitol-1,4-cyclic sulfate, followed by deprotection with trifluoroacetic acid. Two of the four compounds inhibit recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with Ki values of 20+/-4 and 53+/-5 microM.
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PMID:Synthesis and glycosidase inhibitory activities of chain-modified analogues of the glycosidase inhibitors salacinol and blintol. 1735 53

The EtOAc extract of the roots of Glycyrrhiza uralensis exhibited alpha-glucosidase inhibitory activity. Bioassay-guided fractionation resulted in the isolation of an active prenylflavonoid, glycyrrhisoflavone. Its structure was elucidated by NMR and MS analyses. A simple method to prepare glycyrrhisoflavone from the 95% EtOH extract of the roots of G. uralensis was developed by combination of Diaion HP-20 column chromatography (CC), silica gel CC, and preparative HPLC. An HPLC-PDA method was developed for quantitative determination of glycyrrhisoflavone in the roots of G. uralensis. The sample was extracted with MeOH and analyzed using a reversed-phase column with isocratic elution with CH3CN-H2O (0.06% trifluoroacetic acid) (42:58) at a flow rate of 1.2 mL/min, a column temperature of 40 degrees C, and a detection wavelength of 260 nm. The method allowed the determination of glycyrrhisoflavone in the concentration range of 5-500 microg/mL. The relative standard deviation values of the precision and repeatability were 0.3% and 2.0%, respectively. The limits of detection and quantification were 0.5 microg/mL and 5 microg/mL, respectively. The relative recovery rate was 100.2 +/- 1.8%. Based on the validation results, the HPLC determination method was found to be precise, accurate, and time conservative. This method was applied successfully to nine different root samples of G. uralensis. The amounts of glycyrrhisoflavone in these samples were 15-93 mg/100 g of dried powdered plant material.
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PMID:Bioassay-guided isolation and quantification of the alpha-glucosidase inhibitory compound, glycyrrhisoflavone, from Glycyrrhiza uralensis. 2073 38