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Bioorg Med Chem. 2013 Sep 1;21(17):5442-50. doi: 10.1016/j.bmc.2013.06.002. Epub 2013 Jun 11.

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

Author information

1
College of Pharmacy, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, Shaanxi Province 710061, People's Republic of China.

Abstract

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

KEYWORDS:

1-Aminomethyl-β-d-glucopyranoside; Sugar mimic; Synthesis; α-Glucosidase

PMID:
23810673
DOI:
10.1016/j.bmc.2013.06.002
[Indexed for MEDLINE]
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