Discovery and biological evaluation of novel α-glucosidase inhibitors with in vivo antidiabetic effect

We have discovered four novel α-glucosidase inhibitors with in vivo antidiabetic effects by means of a drug design protocol involving the virtual screening with docking simulations, in vitro enzyme assay, and in vivo efficacy test. Discovery of α-glucosidase inhibitors has been actively pursued with...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-07, Vol.18 (13), p.3711-3715
Main Authors: Park, Hwangseo, Hwang, Kyo Yeol, Kim, Young Hoon, Oh, Kyung Hwan, Lee, Jae Yeon, Kim, Keun
Format: Article
Language:English
Subjects:
Acarbose - chemistry
alpha-Glucosidases - chemistry
Animals
Antidiabetic activity
Biological and medical sciences
Catalysis
Chemistry, Pharmaceutical - methods
Diabetes
Diabetes Mellitus - drug therapy
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors - chemistry
Female
General and cellular metabolism. Vitamins
Glycoside Hydrolase Inhibitors
Humans
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - pharmacology
Inhibitor
Medical sciences
Models, Chemical
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Virtual screening
α-Glucosidase
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Summary:We have discovered four novel α-glucosidase inhibitors with in vivo antidiabetic effects by means of a drug design protocol involving the virtual screening with docking simulations, in vitro enzyme assay, and in vivo efficacy test. Discovery of α-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate-mediated diseases. We have identified four novel α-glucosidase inhibitors by means of a drug design protocol involving the structure-based virtual screening under consideration of the effects of ligand solvation in the scoring function and in vitro enzyme assay. Because the newly identified inhibitors reveal in vivo antidiabetic activity as well as a significant potency with more than 70% inhibition of the catalytic activity of α-glucosidase at 50 μM, all of them seem to deserve further development to discover new drugs for diabetes. Structural features relevant to the interactions of the newly identified inhibitors with the active site residues of α-glucosidase are discussed in detail.
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2008.05.056