Yasuhiro MinamiChinami KuriyamaKyoko IkedaAtsushi KatoKenji TakebayashiIsao AdachiGeorge W J FleetAikkarach KettawanTadashi OkamotoNaoki AsanoHokuriku UniversityUniversity of ToyamaUniversity of OxfordMahidol UniversityKobe Gakuin University2018-07-122018-07-122008-03-15Bioorganic and Medicinal Chemistry. Vol.16, No.6 (2008), 2734-2740096808962-s2.0-40949137811https://repository.li.mahidol.ac.th/handle/20.500.14594/18951We 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 μM. 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 μM. 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 μM, and was further a stronger inhibitor of human lysosomal α-glucosidase than the derivative (IC 50 = 0.34 μM). This indicates that the sulfate in the side chain plays an important role in the specificity of enzyme inhibition. © 2008 Elsevier Ltd. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemistryPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.bmc.2008.01.032