Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
| Autor: | Humaira Zafar, M. Iqbal Choudhary, Atia-tul-Wahab, Saeed Ullah, Fatima Z. Basha, Umm-E-Farwa, Munisaa Younus, Maria Aqeel Khan |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Nitrile Stereochemistry Clinical Biochemistry Kinetics Pharmaceutical Science Saccharomyces cerevisiae Oligo-1 6-Glucosidase 01 natural sciences Biochemistry Mice Structure-Activity Relationship chemistry.chemical_compound Dibenzazepines Drug Discovery medicine Animals Hypoglycemic Agents Glycoside Hydrolase Inhibitors Isoxazole Molecular Biology Enzyme Assays Acarbose chemistry.chemical_classification Cycloaddition Reaction Molecular Structure 010405 organic chemistry Chemistry α glucosidase Organic Chemistry 3T3 Cells Isoxazoles Cycloaddition 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Enzyme Molecular Medicine Protein Binding medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 40:127979 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2021.127979 |
| Popis: | α-Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33–54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α-glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α-glucosidase (EC 3.2.1.20) enzyme (IC50 = 35.62 ± 1.48 to 333.30 ± 1.67 µM) using acarbose as a reference drug (IC50 = 875.75 ± 2.08 µM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33, 40, 41, 46, 48–50, and 54 showed binding interactions with critical amino acid residues of α-glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect