Design, synthesis and in vitro study of densely functionalized oxindoles as potent α-glucosidase inhibitors
| Autor: | A. Uma, Rahul Agarwal, Tania Luthra, K. Naga Lalitha, Subhabrata Sen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Stereochemistry Clinical Biochemistry Pharmaceutical Science 01 natural sciences Biochemistry Molecular Docking Simulation Inhibitory Concentration 50 Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Non-competitive inhibition Yeasts Drug Discovery Humans Structure–activity relationship Glycoside Hydrolase Inhibitors Oxindole Homology modeling Molecular Biology IC50 chemistry.chemical_classification 010405 organic chemistry Organic Chemistry alpha-Glucosidases Yeast Oxindoles 0104 chemical sciences Kinetics 030104 developmental biology Enzyme Diabetes Mellitus Type 2 chemistry Drug Design Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry. 26:4996-5005 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2018.08.022 |
| Popis: | Diabetes a non-communicable disease occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicated an increase in the trend of people diagnosed with type 2 diabetes mainly due to unhealthy life style. Here in we report a new class of oxindole derivatives 6a-k via scaffold hopping of known α-glucosidase inhibitors 1–4. When molecular docking was performed against a homology model of α-glucosidase the resulting compound 6d revealed binding interactions comparable to 1–4. The compounds were accessed through a unique condensation-ring opening protocol of pyridofuranone building blocks. Overall the compounds exhibited decent binding to the yeast α-glucosidase, where the most potent compound 6h, inhibited the enzyme with IC50 of 0.6 µM. This was nearly threefold improvement from the original known compounds 1–4, selected to design the newer analogs. The reaction kinetics of 6h indicated competitive inhibition. |
| Databáze: | OpenAIRE |
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