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Discovery of novel alpha-glucosidase inhibitors based on the virtual screening with the homology-modeled protein structure
- Source :
- Bioorganicmedicinal chemistry. 16(1)
- Publication Year :
- 2007
-
Abstract
- Discovery of alpha-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 been able to identify 13 novel alpha-glucosidase inhibitors by means of a computer-aided drug design protocol involving homology modeling of the target protein and the virtual screening with docking simulations under consideration of the effects of ligand solvation in the binding free energy function. Because the newly discovered inhibitors are structurally diverse and reveal a significant potency with IC(50) values lower than 50 microM, all of them can be considered for further development by structure-activity relationship studies or de novo design methods. Structural features relevant to the interactions of the newly identified inhibitors with the active site residues of alpha-glucosidase are discussed in detail.
- Subjects :
- Molecular model
Clinical Biochemistry
Pharmaceutical Science
Ligands
Biochemistry
Inhibitory Concentration 50
Structure-Activity Relationship
Protein structure
Drug Discovery
Diabetes Mellitus
Humans
Glycoside Hydrolase Inhibitors
Homology modeling
Enzyme Inhibitors
Molecular Biology
Glucose Metabolism Disorders
Virtual screening
biology
Chemistry
Organic Chemistry
Active site
Enzyme inhibitor
Docking (molecular)
Structural Homology, Protein
Drug Design
biology.protein
Solvents
Molecular Medicine
Computer-Aided Design
Target protein
Protein Binding
Subjects
Details
- ISSN :
- 14643391
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Bioorganicmedicinal chemistry
- Accession number :
- edsair.doi.dedup.....e65dccf58e1f89fafee821b2ac74a34c