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Glucosidase Inhibitors (glucosidase + inhibitor)
Selected AbstractsSynthesis of New C(2) -Substituted gluco -Configured Tetrahydroimidazopyridines and Their Evaluation as Glucosidase InhibitorsHELVETICA CHIMICA ACTA, Issue 10 2005Bhagavathy Shanmugasundaram The gluco -configured C(2) -substituted tetrahydroimidazopyridines 8,14 were prepared and tested as inhibitors of the , -glucosidases from Caldocellum saccharolyticum and from sweet almonds, and of the , -glucosidase from brewer's yeast. All new imidazopyridines are nanomolar inhibitors of the , -glucosidases and micromolar inhibitors of the , -glucosidase. The 3-phenylpropyl derivative 14 proved the strongest inhibitor of the Caldocellum , -glucosidase (Ki,=,0.9,nM), only slightly weaker than the known 2-phenylethyl analogue 7, and the propyl derivative 13 is the strongest inhibitor of the sweet almond , -glucosidases (Ki,=,3.2,nM), again slightly weaker than 7. There is no strong dependence of the inhibition on the nature of the C(2) -substituent and no clear correlation between the inhibitory strength of the known manno -configured imidazopyridines 2,6 and the gluco -analogues 8,12. While most manno -imidazopyridines are competitive inhibitors, the gluco -analogues proved non-competitive inhibitors of the Caldocellum , -glucosidase and mixed-type or partial mixed-type inhibitors of the sweet almond , -glucosidases. [source] First Asymmetric Total Synthesis of Penarolide Sulfate A1EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 36 2008Debendra K. Mohapatra Abstract Penarolide sulfate A1, with three contiguous stereogenic centers on a macrocyclic skeleton, affords promise as an ,-glucosidase inhibitor. Herein, we describe the first asymmetric total synthesis of this natural product. A stereoselective strategy for rapid assembly of the complete framework of the 30-membered macrocyclic core is delineated herein. Sequential amidation and intramolecular Sonogashira cross-coupling reactions were pivotal to the success of our efforts. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Inhibition of recombinant human maltase glucoamylase by salacinol and derivativesFEBS JOURNAL, Issue 12 2006Elena J. Rossi Inhibitors targeting pancreatic ,-amylase and intestinal ,-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an ,-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective ,-glucosidase inhibitors modeled after salacinol, a naturally occurring ,-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity. [source] Dolichandroside A, a new , -glucosidase inhibitor and DPPH free-radical Scavenger from Dolichandrone falcata seemPHYTOTHERAPY RESEARCH, Issue 4 2009P. Aparna Abstract A new phenylpropanoid glycoside, dolichandroside-A, together with seven known compounds , -lapachone, lapachol, aloesaponarin II, 8-hydroxydehydroiso- , -lapachone, , -sitosterol, 3,8-dihydroxydehydroiso- , -lapachone and verbascoside were isolated from the active ethyl acetate soluble extract of heartwood of Dolichandrone falcata. All except for dolichandroside-A are known compounds, but have been isolated for the first time from this plant. The structure of all these compounds was determined on the basis of 1D- and 2D-NMR spectral data. All the isolates were tested for , -glucosidase inhibitory and DPPH radical scavenging activity. This is the first report identifying DPPH scavenging activity and , -glucosidase inhibitory activity in D. falcata. Furthermore, along with a new compound, dolichandroside-A, this study also assigns for the first time , -glucosidase inhibitory activity to verbascoside and aloe saponarin-II. Copyright © 2008 John Wiley & Sons, Ltd. [source] The anti-diabetic drug miglitol is protective against anginal ischaemia through a mechanism independent of regional myocardial blood flow in the dogCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2005Yoshihiro Uno SUMMARY 1.,In the present study, we attempted to clarify whether the antidiabetic drug miglitol, an ,-glucosidase inhibitor, has a protective effect against anginal ischaemia. We had reported previously that miglitol reduces myocardial infarct size through inhibition of glycogenolysis during ischaemia in rabbits. However, the effect of miglitol on anginal ischaemia remains unknown. 2.,In open-chest beagle dogs with a severely stenosed left anterior descending coronary artery, an epicardial electrode was attached to the surface of the risk area of the left ventricle and a microdialysis probe was implanted into the myocardium to measure ST segment changes and interstitial lactate accumulation. The first episode of anginal ischaemia was induced by atrial pacing and phenylephrine infusion (50,100 µg/min) for 10 min. The second episode of anginal ischaemia was induced 210 min after the first episode. Miglitol (10 mg/kg, i.v.) was administered to the miglitol group (n = 10) 30 min before the second episode of anginal ischaemia, whereas saline was administered to the control group (n = 10). Regional myocardial blood flow was measured using coloured microspheres. 3.,There was no significant difference in regional myocardial blood flow in the risk and non-risk areas between the first and second episodes of anginal ischaemia and between the miglitol and control groups. During the first and second episodes of anginal ischaemia, the ST segment was decreased to a similar extent in the control group. Although ST segment depression during the first episode of anginal ischaemia was similar in both groups, ST segment depression during the second episode of anginal ischaemia was significantly attenuated in the miglitol-treated group compared with the control group (1.3 ± 0.4 vs 2.2 ± 0.4 mV, respectively). Miglitol significantly attenuated myocardial interstitial lactate accumulation in the risk area. 4.,In conclusion, in the present study miglitol improved ST segment depression and attenuated the accumulation of myocardial interstitial lactate during anginal ischaemia without altering regional myocardial blood flow. Miglitol has an anti-anginal ischaemia effect via a mechanism that is independent of regional myocardial blood flow. [source] Inhibition of recombinant human maltase glucoamylase by salacinol and derivativesFEBS JOURNAL, Issue 12 2006Elena J. Rossi Inhibitors targeting pancreatic ,-amylase and intestinal ,-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an ,-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective ,-glucosidase inhibitors modeled after salacinol, a naturally occurring ,-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity. [source] GLYCOSIDASE INHIBITORY ACTIVITY AND ANTIOXIDANT PROPERTIES OF A POLYSACCHARIDE FROM THE MUSHROOM INONOTUS OBLIQUUSJOURNAL OF FOOD BIOCHEMISTRY, Issue 2010HAIXIA CHEN ABSTRACT A water-soluble polysaccharide from Inonotus obliquus (IOPS) was isolated from the mushroom Inonotus obliquus (Fr.) Pilat. The chemical compositions, molecular weight and inhibitory activities on glycosidase and antioxidant properties of IOPS were investigated. The results indicated that IOPS was an acid protein-bound polysaccharide, with a molecular weight of 1.7 × 104 Da and the contents of neutral sugar, protein and uronic acids being 42.5, 18.5 and 6.1%, respectively. IOPS exhibited an inhibitory activity against ,-glucosidase with the IC50 value of 93.3 µg/mL, whereas it had no effective inhibition on ,-amylase. Results of antioxidant activity assays revealed that IOPS had inhibitory activity on the concentration-dependent quenching of 1,1-Diphenyl-2-picrylhydrazyl and hydroxyl radicals. Furthermore, IOPS inhibited the formation of thiobarbituric acid-reactive substances in Fe2+/ascorbate-induced lipid peroxidation in rat liver tissue. These results clearly demonstrated that IOPS was one of the main bioactive components of I. obliquus that contributed to hypoglycemic activity and antioxidant activity. PRACTICAL APPLICATIONS Diabetes mellitus is one of the primary threats to human health because of its increasing prevalence, chronic course and disabling complications. Postprandial hyperglycemia plays an important role in the development of type 2 diabetes mellitus and complications associated with the disease. One therapeutic approach to decrease postprandial hyperglycemia is to retard the absorption of glucose through inhibition of carbohydrate-hydrolyzing enzymes in the digestive organs. In this study, a polysaccharide isolated from the mushroom Inonotus obliquus (IOPS) was shown to have notable glycosidase inhibitory effects and antioxidant activities. This research will benefit for the investigation of effective and safe ,-glucosidase inhibitors from natural materials. IOPS could be a good candidate for application in food and medicinal fields. It might be developed for functional food or lead compounds for use in antidiabetes. [source] INHIBITORY POTENTIAL OF WINE AND TEA AGAINST ,-AMYLASE AND ,-GLUCOSIDASE FOR MANAGEMENT OF HYPERGLYCEMIA LINKED TO TYPE 2 DIABETESJOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2008YOUNG-IN KWON ABSTRACT Natural ,-amylase and ,-glucosidase inhibitors from food-grade plants offer an attractive strategy to manage postprandial hyperglycemia for type 2 diabetes management via control of starch breakdown and intestinal glucose absorption. In this study, four random sources of red and white wines as well as four types of teas were investigated for ,-amylase and ,-glucosidase inhibitory potential. Water extracts of black tea had the highest ,-glucosidase inhibitory activity, followed by white tea and oolong tea. All the randomly selected red wines had significant ,-glucosidase inhibitory activity compared to white wine. The ,-glucosidase inhibitory activity of the tea and wines correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. Further, these extracts had less or no ,-amylase inhibitory activity, indicating potential to overcome the side effects of undigested starch. This research has relevance for managing hyperglycemia and related oxidation-linked dysfunction and concurrently reducing problems of undigested starch. PRACTICAL APPLICATIONS In this study anti-diabetic-relevant potential of wines and teas were confirmed in four types of red and white wines as well as four types of commonly available teas using in vitro enzyme assays for alpha-glucosidase and alpha-amylase inhibitory activities. In vitro inhibitory activities of these enzymes provide a strong biochemical rationale for further in vivo studies and dietary management strategy for type 2 diabetes through the control of glucose absorption. Further this phenolic antioxidant-enriched dietary strategy using specific beverage combinations can generate a whole food profile that has the potential to reduce hyperglycemia-induced pathogenesis and also associated complications linked to cellular oxidation stress. [source] Identification of ,-glucosidase inhibitors from a new fermented tea obtained by tea-rolling processing of loquat (Eriobotrya japonica) and green tea leavesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2010Asami Toshima Abstract BACKGROUND: A new fermented tea produced by tea-rolling processing of loquat (Eriobotrya japonica) leaf with green tea leaf (denoted as LG tea) showed a potent antihyperglycaemic effect in maltose-loaded rats. The aim of this study, therefore, was to identify ,-glucosidase inhibitors in the antihyperglycaemic tea product. RESULTS: LG tea had a threefold higher maltase-inhibitory activity (IC50 0.065 mg dried extract mL,1) than either the constituent loquat leaf or green tea alone. In addition, LG tea favourably inhibited maltase action rather than sucrase action. As a result of bio-guided high-performance liquid chromatography separations of LG tea, theasinensin A, theasinensin B, strictinin and 1,6-digalloylglucose were newly identified as maltase inhibitors with IC50 values of 142, 225, 398 and 337 µmol L,1 respectively, along with previously identified catechins and theaflavins. CONCLUSION: Judging from the magnitude of the ,-glucosidase-inhibitory contribution of each isolated compound to the overall inhibition of LG tea, catechins were the main candidates responsible for ,-glucosidase or maltase inhibition in LG tea, followed by theaflavins, theasinensins, strictinin and 1,6-digalloylglucose. Copyright © 2010 Society of Chemical Industry [source] Daily consumption of Reliv GlucaffectÔ for 8 weeks significantly lowered blood glucose and body weight in 50 subjectsPHYTOTHERAPY RESEARCH, Issue 12 2009Gianni Belcaro Abstract A public change to healthier lifestyles with more physical activity and better nutrition, including caloric restriction, is required to address the obesity epidemic. Weight loss can be achieved by caloric restrictions; current research suggests that this may be achieved by consumption of slowly absorbed carbohydrates owing to the resulting prolonged satiety. Our rationale was to prolong the satiety of overweight volunteers by supplementation with a proprietary formulation GlucaffectÔ which delays absorption of carbohydrates. GlucaffectÔ provides potent , -glucosidase inhibitors of herbal source such Pycnogenol®, MadeglucylÔ and various others which obstruct absorption of carbohydrates, such as starch. Fifty overweight subjects received either GlucaffectÔ or an inactive control product for eight weeks. Consumption of GlucaffectÔ was found to statistically significantly lower blood-fasting glucose from baseline 145.3 mg/dL to 101.1 mg/dL (,30.4%) and Hba1c from 7.59% to 6.33% as compared to the control group where values decreased only marginally. The weight and the body mass index (BMI) decreased significantly from an average of 88.5 kg (BMI 26.8 kg/m2) to 81.3 kg (BMI 24.5 kg/m2) as compared to the control group. In conclusion, GlucaffectÔ enabled subjects with metabolic syndrome to achieve healthy BMI and blood glucose levels. GlucaffectÔ was well tolerated and no subject dropped out. Copyright © 2009 John Wiley & Sons, Ltd. [source] Molecular Basis for ,-Glucosidase Inhibition by Ring-Modified Calystegine AnaloguesCHEMBIOCHEM, Issue 16 2008Matilde Aguilar Neutral calystegine B2analogues, such as the 1-deoxy-6-oxa- N -(N, -octyl)thiocarbamoyl derivative, proved to be more potent ,-glucosidase inhibitors than the natural alkaloid. Structural studies of the complex with a clan GH-A ,-glucosidase from Thermotoga maritima showed a binding mode markedly different from that of the parent compound. [source] Anomer-Selective Glycosidase Inhibition by 2- N -Alkylated 1-AzafagominesCHEMBIOCHEM, Issue 6 2007Oscar Lopez Lopez Dr. Abstract Alkylation of 1-azafagomine at the 2-N position was achieved by reductive amination of 1- N -acetyl-3,4,6-tri- O -benzyl-1-azafagomine by using aldehydes, palladium hydroxide, and hydrogen in EtOAc/water/acetic acid followed by deprotection. The 2-N-butyl, hexyl, heptyl, nonyl, decyl, and 3-phenylpropyl derivatives were made in this manner, and were tested for inhibition of ,-glucosidase from yeast, and of ,-glucosidase from almonds. The new compounds were stronger ,-glucosidase inhibitors than 1-azafagomine, but weaker ,-glucosidase inhibitors. [source] | |||||||||||||