title: Effect of five-membered sugar mimics on mammalian glycogen-degrading enzymes and various glucosidases.
abstract: We investigated inhibitory activities of five-membered sugar mimics toward glycogen-degrading enzymes and a variety of glucosidases. 1,4-Dideoxy-1,4-imino-D-arabinitol (D-AB1) is known to be a potent inhibitor of glycogen phosphorylase. However, the structural modification of D-AB1, such as its enantiomerization, epimerization at C-2 and/or C-3, introduction of a substituent to C-1, and replacement of the ring nitrogen by sulfur, markedly lowered or abolished its inhibition toward the enzyme. The present work elucidated that d-AB1 was also a good inhibitor of the de-branching enzyme of glycogen, amylo-1,6-glucosidase, with a IC(50) value of 8.4 microM. In the present work, the de-sulfonated derivative of salacinol was isolated from the roots of Salacia oblonga and found to be a potent inhibitor of rat intestinal isomaltase with an IC(50) value of 0.64 microM. On the other hand, salacinol showed a much more potent inhibitory activity toward maltase in Caco-2 cell model system than its de-sulfonated derivative, with an IC(50) value of 0.5 microM, and was further a stronger inhibitor of human lysosomal alpha-glucosidase than the derivative (IC(50)=0.34 microM). This indicates that the sulfate in the side chain plays an important role in the specificity of enzyme inhibition.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Minami
authors.forename: Chinami
authors.initials: C
authors.lastname: Kuriyama
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ikeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Kenji
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Adachi
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet
authors.forename: Aikkarach
authors.initials: A
authors.lastname: Kettawan
authors.forename: Tadashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Asano
mesh_terms: D000818:Animals; D001089:Arabinose / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D018716:Molecular Mimicry; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D001089:Arabinose; D005959:Glucosidases