کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1361136 | 981458 | 2008 | 7 صفحه PDF | دانلود رایگان |
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 IC50 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 IC50 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 IC50 value of 0.5 μM, and was further a stronger inhibitor of human lysosomal α-glucosidase than the derivative (IC50 = 0.34 μM). This indicates that the sulfate in the side chain plays an important role in the specificity of enzyme inhibition.
Anti-hyperglyceamic effect of D-AB 1 on oh/oh mice reported maybe due to a combination of glycogen phosphorylase and amylo-1 ,6-glucosidase inhibition. The sufate in the side chain of salacinol plays an important role in the specificity of enzyme inhibition.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 6, 15 March 2008, Pages 2734–2740