Synthesis and ¦Á-glucosidase inhibitory activity evaluation of N-substituted aminomethyl-¦Â-d-glucopyranosides

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• 作者：Xiaoli Bian ; Xiangni Fan ; Changhu Ke ; Yajun Luan ; Guilan Zhao ; Aiguo Zeng
• 关键词：¦Á-Glucosidase ; 1-Aminomethyl-¦Â-d-glucopyranoside ; Sugar mimic ; Synthesis
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：21
• 期：17
• 页码：5442-5450
• 全文大小：731 K

文摘

A series of N-substituted 1-aminomethyl-¦Â-d-glucopyranoside derivatives was prepared. These novel synthetic compounds were assessed in vitro for inhibitory activity against yeast ¦Á-glucosidase and both rat intestinal ¦Á-glucosidases maltase and sucrase. Most of the compounds displayed ¦Á-glucosidase inhibitory activity, with IC₅₀ values covering the wide range from 2.3 ¦ÌM to 2.0 mM. Compounds 19a (IC₅₀ = 2.3 ¦ÌM) and 19b (IC₅₀ = 5.6 ¦ÌM) were identified as the most potent inhibitors for yeast ¦Á-glucosidase, while compounds 16 (IC₅₀ = 7.7 and 15.6 ¦ÌM) and 19e (IC₅₀ = 5.1 and 10.4 ¦ÌM) were the strongest inhibitors of rat intestinal maltase and sucrase. Analysis of the kinetics of enzyme inhibition indicated that 19e inhibited maltase and sucrase in a competitive manner. The results suggest that the aminomethyl-¦Â-d-glucopyranoside moiety can mimic the substrates of ¦Á-glucosidase in the enzyme catalytic site, leading to competitive enzyme inhibition. Moreover, the nature of the N-substituent has considerable influence on inhibitory potency.