期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 1, 页码 62-64出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2011.11.084
关键词
alpha-Glucosidase inhibitor; Irreversible inhibitor; In silico; High-throughput screening
资金
- Ministry of Education, Science, Sports and Culture [17790097]
- Ministry of Health, Labour and Welfare, Japan
- Grants-in-Aid for Scientific Research [17790097] Funding Source: KAKEN
5-Thiazoleacetamide derivatives of AR122 and AR125 were screened as alpha-glucosidase inhibitors by in silico high-throughput screening from commercial drug-like small compound libraries. Inhibition of alpha-glucosidase with AR122 and AR125 is time dependent: with no preincubation, AR122 and AR125 are relatively moderate inhibitors, but interestingly, after a 120 min incubation, they were 50-fold more potent (AR122: IC50 = 2.47 mu M and AR125: IC50 = 27.1 mu M). Plots of ln [residual alpha-glucosidase activity %] versus preincubation time show a pseudo-first order kinetics for both inhibitors. Through dialysis of enzyme-inhibitor complexes, no activity recovery was shown. These results suggest that AR122 and AR125 constitute a new class of noncarbohydrate mimetic inhibitor with an irreversible mechanism. (C) 2011 Elsevier Ltd. All rights reserved.
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