Phosphaisocoumarins as a new class of potent inhibitors for pancreatic cholesterol esterase
| Autor: | Hailiang Lu, Baojian Li, Binhua Zhou, Ai-Yun Peng, Lin Ma |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Swine
Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Non-competitive inhibition Drug Discovery Sterol esterase Structure–activity relationship Animals Enzyme Inhibitors Pancreas Pharmacology chemistry.chemical_classification biology Molecular Structure Chemistry Organic Chemistry Stereoisomerism General Medicine Sterol Esterase In vitro Isocoumarin Kinetics Enzyme Biochemistry Isocoumarins Enzyme inhibitor Drug Design biology.protein |
| Zdroj: | European journal of medicinal chemistry. 45(5) |
| ISSN: | 1768-3254 |
| Popis: | Due to the importance of pancreatic cholesterol esterase (CEase) as a potential target in atherosclerosis and for the development of hypocholesterolemic agents, there are increasing interests in designing and synthesizing CEase inhibitors. In the present study, we prepared forty-five isocoumarin phosphorus analogues (i.e., phosphaisocoumarins) and investigated the inhibition of these compounds on the CEase. The results showed that some phosphaisocoumarins could act as potent inhibitors of CEase. The most potent inhibitors, compounds 9d, 10a and 12e give IC50 values of 4.8 microM, 2.3 microM and 1.9 microM, respectively. The inhibition mechanism and kinetic characterization studies indicate that they are reversible competitive inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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