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Exploiting the Therapeutic Potential of 8-β-d-Glucopyranosylgenistein: Synthesis, Antidiabetic Activity, and Molecular Interaction with Islet Amyloid Polypeptide and Amyloid β-Peptide (1-42)
- Publication Year :
- 2014
- Publisher :
- American Chemical Society, 2014.
-
Abstract
- 8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell sensitivity, insulin secretion, and circulating insulin within 7 days at a dose of 4 (mg/kg bw)/day. Suppression of islet amyloid polypeptide (IAPP) fibril formation by compound 1 was demonstrated by thioflavin T fluorescence and atomic force microscopy. Molecular recognition studies with IAPP and Aβ1-42 employing saturation transfer difference (STD) confirmed the same binding mode for both amyloid peptides as suggested by their deduced epitope. Insights into the preferred conformation in the bound state and conformers' geometry resulting from interaction with Aβ1-42 were also given by STD, trNOESY, and MM calculations. These studies strongly support 8-β-d-glucopyranosylgenistein as a promising molecular entity for intervention in amyloid events of both diabetes and the frequently associated Alzheimer's disease.
- Subjects :
- medicine.medical_specialty
Magnetic Resonance Spectroscopy
Protein Conformation
medicine.medical_treatment
Microscopy, Atomic Force
Flavonoids, Alzheimer's, diabete, NMR spectroscopy, AFM, carbohydrates
Streptozocin
Epitope
Diabetes Mellitus, Experimental
Epitopes
chemistry.chemical_compound
Protein structure
Glucosides
Alzheimer Disease
Internal medicine
Drug Discovery
CHIM/06 - CHIMICA ORGANICA
medicine
Animals
Humans
Hypoglycemic Agents
Insulin
Benzothiazoles
Genista
Rats, Wistar
Protein Kinase Inhibitors
geography
Amyloid beta-Peptides
geography.geographical_feature_category
Chemistry
medicine.disease
Islet
Genistein
In vitro
Islet Amyloid Polypeptide
Rats
Oxygen
Thiazoles
Endocrinology
Postprandial
Microscopy, Fluorescence
Biochemistry
Drug Design
Hyperglycemia
Molecular Medicine
Thioflavin
Alzheimer's disease
Protein Binding
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....0452662e66794a5d389a2ad8e19ef545