α- and β-Glucosidase inhibitors: chemical structure and biological activity

Abstract Glycoside trimming enzymes are crucially important in a broad range of metabolic pathways, including glycoprotein and glycolipid processing and carbohydrate digestion in the intestinal tract. Amongst the large array of enzymes, glucosidases are postulated to be a powerful therapeutic target since they catalyze the cleavage of glycosidic bonds releasing glucose from the non-reducing end of an oligo- or polysaccharide chain involved in glycoprotein biosynthesis. Glucosidase inhibitors are currently of interest owing to their promising therapeutic potential in the treatment of disorders such as diabetes, human immunodeficiency virus (HIV) infection, metastatic cancer, and lysosomal storage diseases. Glucosidase inhibitors have also been useful in probing biochemical pathways and understanding structure–activity relationship patterns required for mimicking the enzyme transition state. Amongst the various types of glucosidase inhibitors, disaccharides, iminosugars, carbasugars, thiosugars, and non-sugar derivatives have received great attention. This review is aimed at highlighting the main chemical classes of glucosidase inhibitors, as well as their biological activities toward α- and β-glucosidases, but it is not intended to be an exhaustive review on the subject. Inhibition data on the compounds covered in this review are included in a tabular form as an Appendix, where the type of each glucosidase associated with a specific inhibitor is also given.

[1]  Chi‐Huey Wong.  Carbohydrate-based drug discovery. , 2003 .

[2]  P. Compain,et al.  Synthesis and biological evaluation of the first example of an eight-membered iminoalditol , 2004 .

[3]  S. Withers,et al.  Powerful probes for glycosidases: novel, fluorescently tagged glycosidase inhibitors. , 2001, Bioorganic & medicinal chemistry letters.

[4]  Taisuke Uehara,et al.  Callyspongynic acid, a polyacetylenic acid which inhibits alpha-glucosidase, from the marine sponge Callyspongia truncata. , 2002, Journal of natural products.

[5]  M. Kiso,et al.  Studies on 1-Deoxynojirimycin-Containing Glycans: Synthesis of Novel Disaccharides Related to Lactose, Lactosamine, and Chitobiose , 1992 .

[6]  B. Svensson,et al.  Synthesis of nitrogen analogues of salacinol and their evaluation as glycosidase inhibitors. , 2001, Journal of the American Chemical Society.

[7]  C. Wünsche,et al.  Untersuchungen zur struktur des α-d-glucosidaseinhibitors acarbose☆ , 1984 .

[8]  G. Kite,et al.  α-Homonojirimycin [2,6-dideoxy-2,6-imino-d-glycero-l-gulo-heptitol] from omphalea diandra L.: isolation and glucosidase inhibtion , 1988 .

[9]  R. Dwek,et al.  The combination of interferon alpha-2b and n-butyl deoxynojirimycin has a greater than additive antiviral effect upon production of infectious bovine viral diarrhea virus (BVDV) in vitro: implications for hepatitis C virus (HCV) therapy. , 2002, Antiviral research.

[10]  Recent advances in the chemistry of azapyranose sugars , 2005 .

[11]  B. Svensson,et al.  Synthesis of selenium analogues of the naturally occurring glycosidase inhibitor salacinol and their evaluation as glycosidase inhibitors. , 2002, Journal of the American Chemical Society.

[12]  A. Arcelli,et al.  Synthesis of new enantiopure thiepane derivatives and their evaluation as glycosidase inhibitors , 2002 .

[13]  H. Hashimoto,et al.  Synthesis of salacinol , 2000 .

[14]  Markolf Hanefeld,et al.  Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. , 2003, JAMA.

[15]  Y. Igarashi,et al.  An extremely potent inhibitor for β-galactosidase , 1995 .

[16]  A. Aubertin,et al.  Stereoisomeric Imidazolo‐Pentoses − Synthesis, Chiroptical Properties, and Evaluation as Glycosidase Inhibitors , 2001 .

[17]  G. Papandreou,et al.  Mimicking the glucosidase transition state : shape/charge considerations , 1991 .

[18]  H. Matsuura,et al.  α-Glucosidase Inhibitor from the Seeds of Balsam Pear (Momordica charantia) and the Fruit Bodies of Grifola frondosa , 2002, Bioscience, biotechnology, and biochemistry.

[19]  G. Jacob,et al.  Glycosylation inhibitors in biology and medicine. , 1995, Current opinion in structural biology.

[20]  E. Clercq,et al.  Design of Anti-AIDS Drugs , 1990 .

[21]  S. K. Chung,et al.  Facile synthetic routes to all possible enantiomeric pairs of conduritol stereoisomers via efficient enzymatic resolution of conduritol B and C derivatives. , 2001, Organic letters.

[22]  M. Watanabe,et al.  Synthesis and α-Glucosidase-Inhibiting Activity of a New α-Glucosidase Inhibitor, 4-O-α-D-Glucopyranosylmoranoline and Its N-Substituted Derivatives , 1989 .

[23]  Yuichi Hashimoto,et al.  Novel α-glucosidase inhibitors with a tetrachlorophthalimide skeleton , 2000 .

[24]  G. Dangschat,et al.  Über die Konstitution des Condurits und über einige Cyclohexantetrole , 1939, Naturwissenschaften.

[25]  K. Matsui,et al.  Homonojirimycin Isomers and Glycosides from Aglaonema treubii , 1997 .

[26]  G. Papandreou,et al.  Potent, broad-spectrum inhibition of glycosidases by an amidine derivative of D-glucose , 1990 .

[27]  J. Kanfer,et al.  The Gaucher mouse. , 1975, Biochemical and biophysical research communications.

[28]  K. Yasuda,et al.  New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica. , 2002, Journal of natural products.

[29]  H. Ploegh,et al.  Chemical modification of the glucosidase inhibitor 1-deoxynojirimycin. Structure-activity relationships. , 1991, The Journal of biological chemistry.

[30]  J. Marco-Contelles.  Cyclohexane Epoxides − Chemistry and Biochemistry of (+)‐Cyclophellitol , 2001 .

[31]  Yuguo Zheng,et al.  Properties and production of valienamine and its related analogues. , 2003, Chemical reviews.

[32]  A. Reitz,et al.  Pharmacological treatment of obesity: therapeutic strategies. , 1999, Journal of medicinal chemistry.

[33]  A. Watson,et al.  Therapeutic applications of sugar-mimicking glycosidase inhibitors. , 2001, Mini reviews in medicinal chemistry.

[34]  M. Wormald,et al.  Polyhydroxylated pyrrolidine and pyrrolizidine alkaloids from Hyancinthoides non-scripta and Scilla campanulata. , 1999, Carbohydrate research.

[35]  B. Walker,et al.  Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Kawabata,et al.  6-Hydroxyflavonoids as α-Glucosidase Inhibitors from Marjoram (Origanum majorana) Leaves , 2003 .

[37]  Troels Skrydstrup,et al.  Isofagomine, a potent, new glycosidase inhibitor , 1994 .

[38]  M. Wolfrom,et al.  DEGRADATION OF AMYLOPECTIN TO NIGEROSE , 1955 .

[39]  A. Watson,et al.  Polyhydroxylated alkaloids -- natural occurrence and therapeutic applications. , 2001, Phytochemistry.

[40]  E. Shanmugasundaram,et al.  Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre, R.Br. , 1983, Journal of ethnopharmacology.

[41]  R. Dwek,et al.  Secretion of human hepatitis B virus is inhibited by the imino sugar N-butyldeoxynojirimycin. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[42]  K. Matsui,et al.  Nitrogen-in-the-ring pyranoses and furanoses: structural basis of inhibition of mammalian glycosidases. , 1994, Journal of medicinal chemistry.

[43]  T. Okamoto,et al.  Iminosugar-producing Thai medicinal plants. , 2005, Journal of natural products.

[44]  Werner Frommer,et al.  Chemistry and Biochemistry of Microbial α‐Glucosidase Inhibitors , 1981 .

[45]  B. Svensson,et al.  Synthesis of alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol analogues: polar side-chain modification, sulfonium and selenonium heteroatom variants, conformational analysis, and evaluation as glycosidase inhibitors. , 2004, Journal of the American Chemical Society.

[46]  M. Kieny,et al.  The alpha-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step. , 2002, Molecular pharmacology.

[47]  M. Salvucci.  Effect of the alpha-glucosidase inhibitor, bromoconduritol, on carbohydrate metabolism in the silverleaf whitefly, Bemisia argentifolii. , 2000, Archives of insect biochemistry and physiology.

[48]  Wolfgang Liebl,et al.  Crystal structure of Thermotoga maritima 4-alpha-glucanotransferase and its acarbose complex: implications for substrate specificity and catalysis. , 2002, Journal of molecular biology.

[49]  K. Matsui,et al.  N-containing sugars from Morus alba and their glycosidase inhibitory activities. , 1994, Carbohydrate research.

[50]  H. Matsuda,et al.  Salacinol, potent antidiabetic principle with unique thiosugar sulfonium sulfate structure from the Ayurvedic traditional medicine Salacia reticulata in Sri Lanka and India , 1997 .

[51]  K. Matsumoto,et al.  Inhibition of experimental metastasis by castanospermine in mice: blockage of two distinct stages of tumor colonization by oligosaccharide processing inhibitors. , 1986, Cancer research.

[52]  C. Huxtable,et al.  A Spectroscopic Investigation of Swainsonine: An α-Mannosidase Inhibitor Isolated from Swainsona canescens , 1979 .

[53]  M. Humphries,et al.  Oligosaccharide modification by swainsonine treatment inhibits pulmonary colonization by B16-F10 murine melanoma cells. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[54]  K. Matsui,et al.  Valienamine as an alpha-glucosidase inhibitor. , 1980, The Journal of antibiotics.

[55]  J. Hanson,et al.  Transition state structure of purine nucleoside phosphorylase and principles of atomic motion in enzymatic catalysis. , 2001, Biochemistry.

[56]  P. Vogel,et al.  Amino(hydroxymethyl)cyclopentanetriols, an Emerging Class of Potent Glycosidase Inhibitors—Part I: Synthesis and Evaluation of β‐D‐Pyranoside Analogues in the manno, gluco, galacto, and GlcNAc Series , 2001, Chembiochem : a European journal of chemical biology.

[57]  A. Watson,et al.  Alkaloidal components in the poisonous plant, Ipomoea carnea (Convolvulaceae). , 2003, Journal of agricultural and food chemistry.

[58]  H. Hara,et al.  Studies on the alpha-glucoside hydrolase inhibitor, adiposin. III. alpha Glucoside hydrolase inhibitory activity and antibacterial activity in vitro. , 1982, The Journal of antibiotics.

[59]  A. Sjoerdsma,et al.  ANTI-HIV ACTIVITY OF CASTANOSPERMINE ANALOGUES , 1989, The Lancet.

[60]  P. Tyler,et al.  New syntheses of 1D- and 1L-1,2-anhydro-myo-inositol and assessment of their glycosidase inhibitory activities. , 2000, Carbohydrate research.

[61]  B. M. Pinto,et al.  A new class of glycosidase inhibitor: synthesis of salacinol and its stereoisomers. , 2001, The Journal of organic chemistry.

[62]  S. Matsunaga,et al.  Penarolide Sulfates A1 and A2, New α-Glucosidase Inhibitors from a Marine Sponge Penares sp. , 2000 .

[63]  T. Takeuchi,et al.  All eight stereoisomeric D-glyconic-delta-lactams: synthesis, conformational analysis, and evaluation as glycosidase inhibitors. , 2000, Journal of Organic Chemistry.

[64]  D. Leaback.  On the inhibition of beta-N-acetyl-D-glucosaminidase by 2-acetamido-2-deoxy-D-glucono-(1-5)-lactone. , 1968, Biochemical and biophysical research communications.

[65]  C. Ortiz Mellet,et al.  Castanospermine-trehazolin hybrids: a new family of glycomimetics with tuneable glycosidase inhibitory properties. , 2002, Chemical communications.

[66]  M. Ogawa,et al.  New alpha-amylase inhibitor, trestatins. III. Structure determination of new trestatin components Ro 09-0766, Ro 09-0767 and Ro 09-0768. , 1984, The Journal of antibiotics.

[67]  G. Mehta,et al.  Polycyclitols. Novel conduritol and carbasugar hybrids as a new class of potent glycosidase inhibitors , 2000 .

[68]  G. Papandreou,et al.  A new family of five-carbon iminoalditols which are potent glycosidase inhibitors , 1990 .

[69]  Isotope edited NMR studies of glycosidases: design and synthesis of a novel glycosidase inhibitor. , 1999, Bioorganic & medicinal chemistry letters.

[70]  R. Dwek,et al.  Therapeutic applications of imino sugars in lysosomal storage disorders. , 2003, Current topics in medicinal chemistry.

[71]  B. Henrissat,et al.  Evolutionary and mechanistic relationships between glycosidases acting on α- and β-bonds☆ , 2005 .

[72]  K. Umezawa,et al.  Biological activities of cyclophellitol. , 1990, The Journal of antibiotics.

[73]  G. Papandreou,et al.  Amidine, amidrazone, and amidoxime derivatives of monosaccharide aldonolactams: synthesis and evaluation as glycosidase inhibitors , 1993 .

[74]  Y. Suhara,et al.  NEW α-AMYLASE INHIBITOR, TRESTATINS , 1983 .

[75]  N. Westergaard,et al.  Iminosugars: potential inhibitors of liver glycogen phosphorylase. , 2001, Bioorganic & medicinal chemistry.

[76]  I. Carvalho,et al.  N-Linked carba-disaccharides as potential inhibitors of glucosidases I and II , 1999 .

[77]  M. Schuster,et al.  Inhibition of fucosyltransferase V by a GDP-Azasugar. , 2001, Bioorganic & medicinal chemistry letters.

[78]  L. James,et al.  Loco intoxication: indolizidine alkaloids of spotted locoweed (Astragalus lentiginosus). , 1982, Science.

[79]  V. Jäger,et al.  Amino(hydroxymethyl)cyclopentanetriols, an Emerging Class of Potent Glycosidase Inhibitors—Part II: Synthesis, Evaluation, and Optimization of β‐D‐Galactopyranoside Analogues , 2001, Chembiochem : a European journal of chemical biology.

[80]  Y. Nakano,et al.  Effect of conduritol A, a polyol from Gymnema sylvestre, on the development of diabetic cataracts in streptozotocin-treated rats and on aldose reductase , 1994 .

[81]  Carlos H. Tomich P. Silva,et al.  Homology modeling and molecular interaction field studies of α-glucosidases as a guide to structure-based design of novel proposed anti-HIV inhibitors , 2005, J. Comput. Aided Mol. Des..

[82]  K. Umezawa,et al.  Production, isolation and structure determination of a novel beta-glucosidase inhibitor, cyclophellitol, from Phellinus sp. , 1990, The Journal of antibiotics.

[83]  A. H. Haines.  Synthesis of a novel pseudodisaccharide glycoside as a potential glycosidase inhibitor , 1998 .

[84]  G. Kaushal,et al.  6,7-Diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase. , 1991, Biochemistry.

[85]  T. Hudlický,et al.  New oligomers of conduritol-F and muco-inositol. Synthesis and biological evaluation as glycosidase inhibitors. , 2004, Bioorganic & medicinal chemistry letters.

[86]  K. Umezawa,et al.  Enantiospecific synthesis and biological evaluation of 1,6-epi-cyclophellitol. , 1991, The Journal of antibiotics.

[87]  E. Bause,et al.  Characterization of calf liver glucosidase I and its inhibition by basic sugar analogs. , 1986, Archives of biochemistry and biophysics.

[88]  F. Leeper,et al.  Synthesis of β-1-homonojirimycin and β-1-homomannojirimycin using the enzyme aldolase , 1994 .

[89]  M. Foglietti,et al.  Synthesis of azasugars as potent inhibitors of glycosidases. , 1997, Bioorganic & medicinal chemistry.

[90]  K. Tsuda,et al.  Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats. , 2003, Diabetes research and clinical practice.

[91]  R. Dwek,et al.  Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses. , 2005, Glycobiology.

[92]  M. Ettlinger,et al.  Nojirimycin and d-glucono-1,5-lactone as inhibitors of carbohydrases , 1971 .

[93]  L. Pickering,et al.  An approach to combinatorial library generation of galactofuranose mimics as potential inhibitors of mycobacterial cell wall biosynthesis: Synthesis of a peptidomimetic of uridine 5′-diphosphogalactofuranose (UDP-Galf) , 1999 .

[94]  Y. Nishimura.  gem-Diamine 1-N-iminosugars and related iminosugars, candidate of therapeutic agents for tumor metastasis. , 2003, Current topics in medicinal chemistry.

[95]  P. Compain,et al.  Carbohydrate mimetics-based glycosyltransferase inhibitors. , 2001, Bioorganic & medicinal chemistry.

[96]  Xiao-Fang Yu,et al.  Characterization of the Biosynthesis of Human Immunodeficiency Virus Type 1 Env from Infected T-cells and the Effects of Glucose Trimming of Env on Virion Infectivity* , 2001, The Journal of Biological Chemistry.

[97]  K. Kabayama,et al.  Convenient synthesis and evaluation of glycosidase inhibitory activity of α- and β-galactose-type valienamines, and some N-alkyl derivatives , 2004 .

[98]  P. Vogel,et al.  Total asymmetric synthesis of (-)-conduramine B-1 and of its enantiomer. N-Benzyl derivatives of conduramine B-1 are beta-glucosidase inhibitors. , 2005, Bioorganic & medicinal chemistry letters.

[99]  A. Vasella,et al.  Recent Insights into Inhibition, Structure, and Mechanism of Configuration-Retaining Glycosidases. , 1999, Angewandte Chemie.

[100]  J. Clardy,et al.  Castanospermine, A 1,6,7,8-tetrahydroxyoctahydroindolizine alkaloid, from seeds of Castanospermum australe , 1981 .

[101]  A. Takatsuki,et al.  Nectrisine is a potent inhibitor of alpha-glucosidases, demonstrating activities similarly at enzyme and cellular levels. , 1996, Biochemical and biophysical research communications.

[102]  R. Ugalde,et al.  Microsomal glucosidases of rat liver. Partial purification and inhibition by disaccharides. , 2005, European journal of biochemistry.

[103]  S. Ploybutr,et al.  Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients. , 2002, Diabetes research and clinical practice.

[104]  P. Desprès,et al.  α-Glucosidase Inhibitors Reduce Dengue Virus Production by Affecting the Initial Steps of Virion Morphogenesis in the Endoplasmic Reticulum , 2000, Journal of Virology.

[105]  S. Withers,et al.  Glycosidase mechanisms: anatomy of a finely tuned catalyst. , 1999, Accounts of chemical research.

[106]  P. D. Lilley,et al.  Homonojirimycin isomers and N-alkylated homonojirimycins: structural and conformational basis of inhibition of glycosidases. , 1998, Journal of medicinal chemistry.

[107]  C. Danzin,et al.  New Potent α-Glucohydrolase Inhibitor MDL 73945 With Long Duration of Action in Rats , 1991, Diabetes.

[108]  T. Mahmud.  The C7N aminocyclitol family of natural products. , 2003, Natural product reports.

[109]  X. Pi-Sunyer,et al.  Acarbose in the Treatment of Type I Diabetes , 1997, Diabetes Care.

[110]  K. Matsui,et al.  Enzymic synthesis of α- and β-d-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities , 1994 .

[111]  G. Kaushal,et al.  Australine, a pyrrolizidine alkaloid that inhibits amyloglucosidase and glycoprotein processing. , 1989, Biochemistry.

[112]  P. Fowler,et al.  Synthesis and activity towards yeast α-glucosidase of 1,5-dideoxy-1,5-imino-L-iditol (1-deoxy-L-idonojirimycin) , 1993 .

[113]  S. Moore,et al.  Perturbation of free oligosaccharide trafficking in endoplasmic reticulum glucosidase I-deficient and castanospermine-treated cells. , 2002, The Biochemical journal.

[114]  S. Murosaki.  Effects of intake of nigerooligosaccharides-supplemented syrup on the immune function and quality of life in the healthy elderly , 2001 .

[115]  S. Matsunaga,et al.  Penasulfate A, a new α-glucosidase inhibitor from a marine sponge Penares sp. , 2004 .

[116]  F. Miedema,et al.  Synthesis of oxygen-substituted N-alkyl 1-deoxynojirimycin derivatives: Aza sugar α-glucosidase inhibitors showing antiviral (HIV-1) and immunosuppressive activity , 1994 .

[117]  M. Arai,et al.  Combination of miglitol, an anti‐diabetic drug, and nicorandil markedly reduces myocardial infarct size through opening the mitochondrial KATP channels in rabbits , 2001, British journal of pharmacology.

[118]  H. Matsuda,et al.  Synthesis of a Nitrogen Analogue of Salacinol and Its α-Glucosidase Inhibitory Activity , 2001 .

[119]  W. Piepersberg,et al.  Biotechnology and molecular biology of the α-glucosidase inhibitor acarbose , 2004, Applied Microbiology and Biotechnology.

[120]  J. Barranger,et al.  Glucocerebrosidase deficiency and lysosomal storage of glucocerebroside induced in cultured macrophages. , 1987, Experimental cell research.

[121]  S. Sabharwal,et al.  N-hydroxyethyl-piperidine and -pyrrolidine homoazasugars: preparation and evaluation of glycosidase inhibitory activity. , 2003, Bioorganic & medicinal chemistry.

[122]  J. Kawabata,et al.  Structure-activity Relationships for α-Glucosidase Inhibition of Baicalein, 5,6,7-Trihydroxyflavone: the Effect of A-Ring Substitution , 2004, Bioscience, biotechnology, and biochemistry.

[123]  C. Spencer,et al.  Miglitol , 2000, Drugs.

[124]  B. Svensson,et al.  NOVEL DISACCHARIDES CONTAINING SULFUR IN THE RING AND NITROGEN IN THE INTERGLYCOSIDE LINKAGE. CONFORMATION OF METHYL 5'-THIO-4-N-ALPHA -MALTOSIDE BOUN D TO GLYCOAMYLASE AND ITS ACTIVITY AS A COMPETITIVE INHIBITOR , 1995 .

[125]  M. Bols,et al.  Noeuromycin, a glycosyl cation mimic that strongly inhibits glycosidases. , 2001, Journal of the American Chemical Society.

[126]  B. M. Pinto,et al.  Synthesis and Conformational Analysis of a Sulfonium-Ion Analogue of the Glycosidase Inhibitor Castanospermine , 2000 .

[127]  W. Piepersberg,et al.  Biosynthesis of the C(7)-cyclitol moiety of acarbose in Actinoplanes species SE50/110. 7-O-phosphorylation of the initial cyclitol precursor leads to proposal of a new biosynthetic pathway. , 2002, The Journal of biological chemistry.

[128]  Chi-Huey Wong,et al.  Carbohydrate Mimetics: A New Strategy for Tackling the Problem of Carbohydrate‐Mediated Biological Recognition , 1999 .

[129]  H. Matsuda,et al.  Kotalanol, a potent alpha-glucosidase inhibitor with thiosugar sulfonium sulfate structure, from antidiabetic ayurvedic medicine Salacia reticulata. , 1998, Chemical & pharmaceutical bulletin.

[130]  B. Axelrod,et al.  1-Aminoglycosides, a new class of specific inhibitors of glycosidases. , 1973, Biochemical and biophysical research communications.

[131]  B. Svensson,et al.  Synthesis and Enzymic Activity of Novel Glycosidase Inhibitors Containing Sulfur and Selenium , 1995 .

[132]  S. Ahn,et al.  Novel α-Glucosidase Inhibitors, CKD-711 and CKD-711a Produced by Streptomyces sp. CK-4416 , 2002 .

[133]  M. I. Khan,et al.  A new access to polyhydroxy piperidines of the azasugar class: synthesis and glycosidase inhibition studies. , 2003, Organic & biomolecular chemistry.

[134]  M. Sinnott,et al.  Catalytic mechanism of enzymic glycosyl transfer , 1990 .

[135]  Isolation of Conduritol A from Gymnema sylvestre and Its Effects against Intestinal Glucose Absorption in Rats , 1993 .

[136]  A. Elbein,et al.  Calystegins, a novel class of alkaloid glycosidase inhibitors. , 1993, Archives of biochemistry and biophysics.

[137]  Dong-Sun Lee.  Dibutyl phthalate, an α-glucosidase inhibitor from Streptomyces melanosporofaciens , 2000 .

[138]  Taisuke Uehara,et al.  Schulzeines A-C, new alpha-glucosidase inhibitors from the marine sponge Penares schulzei. , 2004, Journal of the American Chemical Society.

[139]  M. Bols.  1-Aza Sugars, Apparent Transition State Analogues of Equatorial Glycoside Formation/Cleavage , 1998 .

[140]  Y. Igarashi,et al.  Synthesis of a new inhibitor of α-fucosidase , 1996 .

[141]  Murat Çelik,et al.  Cyclitols: Conduritols and Related Compounds , 2004 .

[142]  M. Sakurai,et al.  Dihydroxynortropane alkaloids from calystegine-producing plants. , 2001, Phytochemistry.

[143]  B. Ganem.  INHIBITORS OF CARBOHYDRATE-PROCESSING ENZYMES : DESIGN AND SYNTHESIS OF SUGAR-SHAPED HETEROCYCLES , 1996 .

[144]  Lei Liu,et al.  Synthesis and partial biological evaluation of a small library of differentially-linked beta-C-disaccharides. , 2003, Journal of Organic Chemistry.

[145]  J. Yon,et al.  The use of inhibitors in the study of glycosidases. , 1982, Biochimie.

[146]  K. Matsui,et al.  Inhibitory effect of pseudo-aminosugars on oligosaccharide glucosidases I and II and on lysosomal alpha-glucosidase from rat liver. , 1990, Journal of Biochemistry (Tokyo).

[147]  C. Ortiz Mellet,et al.  Synthesis and evaluation of isourea-type glycomimetics related to the indolizidine and trehazolin glycosidase inhibitor families. , 2003, The Journal of organic chemistry.

[148]  S. Withers,et al.  Novel, lipophilic derivatives of 2,5-dideoxy-2,5-imino-D-mannitol (DMDP) are powerful beta-glucosidase inhibitors. , 2001, Bioorganic & medicinal chemistry letters.

[149]  G. Legler.  Active site directed inhibitors and mechanism of action of glycosidases , 1973, Molecular and Cellular Biochemistry.

[150]  S. Raptis,et al.  Long‐term effectiveness of a new α‐glucosidase inhibitor (BAY m1099‐miglitol) in insulin‐treated Type 2 diabetes mellitus , 1998 .

[151]  M. Sierks,et al.  Evaluation of isofagomine and its derivatives as potent glycosidase inhibitors. , 1996, Biochemistry.

[152]  A. Elbein,et al.  Inhibitors of pig kidney trehalase. , 1995, Archives of biochemistry and biophysics.

[153]  T. Mahmud,et al.  Biosynthetic studies on the alpha-glucosidase inhibitor acarbose: the chemical synthesis of isotopically labeled 2-epi-5-epi-valiolone analogs. , 2003, Carbohydrate research.

[154]  N. Asano.  Glycosidase inhibitors: update and perspectives on practical use. , 2003, Glycobiology.

[155]  Mikael Bols,et al.  Recent developments of transition-state analogue glycosidase inhibitors of non-natural product origin. , 2002, Chemical reviews.

[156]  K. Kubler.  Beiträge zur Chemie der Kondurangorinde , 2022 .

[157]  M. Arai,et al.  N-methyl-1-deoxynojirimycin (MOR-14), an alpha-glucosidase inhibitor, markedly reduced infarct size in rabbit hearts. , 1998, Circulation.

[158]  S. Colegate,et al.  Polyhydroxy alkaloids: chromatographic analysis. , 2002, Journal of chromatography. A.

[159]  H. Ploegh,et al.  Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase , 1987, Nature.

[160]  H. Kayakiri,et al.  Structure of FR 900483, a new immunomodulator isolated from a fungus , 1988 .

[161]  S. Withers,et al.  Probing the aglycon binding site of a beta-glucosidase: a collection of C-1-modified 2,5-dideoxy-2,5-imino-D-mannitol derivatives and their structure-activity relationships as competitive inhibitors. , 2004, Bioorganic & medicinal chemistry.

[162]  K. Matsui,et al.  N-alkylated nitrogen-in-the-ring sugars: conformational basis of inhibition of glycosidases and HIV-1 replication. , 1995, Journal of medicinal chemistry.

[163]  M. Hanefeld,et al.  Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. , 2004, European heart journal.

[164]  H. Gottlieb,et al.  IOOC Route to Substituted Chiral Pyrrolidines. Potential Glycosidase Inhibitors , 1999 .

[165]  A. Sato,et al.  Kojibiose (2-O-α-D-Glucopyranosyl-D-Glucose): Isolation and Structure: Isolation from Hydrol , 1957, Nature.

[166]  Robert J. Ferrier,et al.  Monosaccharides: Their Chemistry and Their Roles in Natural Products , 1995 .

[167]  H. Mereyala,et al.  Synthesis of conduritols A, (+)-C and (−)-C from D-galactose , 1994 .

[168]  T. Osawa,et al.  Inhibitory activity of corn-derived bisamide compounds against α-glucosidase , 2003 .

[169]  N. Sharon,et al.  Carbohydrates in cell recognition. , 1993, Scientific American.

[170]  G. Legler.  Glycoside hydrolases: mechanistic information from studies with reversible and irreversible inhibitors. , 1990, Advances in carbohydrate chemistry and biochemistry.