Synthesis and characterization of novel, conjugated, fluorescent DNJ derivatives for α-glucosidase recognition

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• 作者：Akihiko Hatano^a ; ^{a-hatano@sic.shibaura-it.ac.jp} ; Yuichi Kanno^a ; Yuya Kondo^a ; Yuta Sunaga^a ; Hatsumi Umezawa^a ; Munehiro Okada^a ; Hideshi Yamada^a ; Ren Iwaki^b ; Atsushi Kato^b ; Koji Fukui^c
• 关键词：Inhibitor ; α-Glucosidase ; DNJ-fluorescent conjugate ; Docking simulation ; IC50
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：25
• 期：2
• 页码：773-778
• 全文大小：791 K
• 卷排序：25

文摘

A series of five new fluorescent deoxynojirimycin (DNJ) conjugates were synthesized and evaluated for their inhibitory effect (IC50) on several α- and β-glucosidases. Three of the conjugates showed enhanced activity. The two synthetic conjugates, DNJ-CF31 and DNJ-Me 2, exhibited improved α-glucosidase inhibitory effects compared to DNJ and miglitol. Interestingly, conjugates 1 and 2 showed strong inhibition of almond-derived β-glucosidase, in contrast to the inhibition tendencies of other inhibitors. Conjugate 5 strongly inhibited rat intestinal maltase, even at 0.10 μM. A docking study indicated that all five conjugates bind to the active site of α-glucosidase (PDB: 3L4V, derived from Homo sapiens). The DNJ portion of the conjugate fits into the cavity of the enzyme, and the fluorescent part locates randomly on the outside surface. Thus, it is likely that these conjugates can specifically recognize intestinal cells, specifically the α-glucosidase on cell membranes.