Synthesis and α-glucosidase inhibitory activity evaluation of N-substituted aminomethyl-β-D-glucopyranosides

A series of N-substituted 1-aminomethyl-beta-D-glucopyranoside derivatives was prepared. These novel synthetic compounds were assessed in vitro for inhibitory activity against yeast a-glucosidase and both rat intestinal a-glucosidases maltase and sucrase. Most of the compounds displayed a-glucosidase inhibitory activity, with IC50 values covering the wide range from 2.3 mu M to 2.0 mM. Compounds 19a (IC50 = 2.31 mu M) and 19b (IC50 = 5.6 mu M) were identified as the most potent inhibitors for yeast a-glucosidase, while compounds 16 (IC50 = 7.7 and 15.6 mu M) and 19e (IC50 = 5.1 and 10.4 mu M) 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-beta-o-glucopyranoside moiety can mimic the substrates of a-glucosidase in the enzyme catalytic site, leading to competitive enzyme inhibition. Moreover, the nature of the N-substituent has considerable influence on inhibitory potency. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.