Structure–activity investigation of the inhibition of 3-hydroxypyridin-4-ones on mammalian tyrosine hydroxylase
| Autor: | Robert C. Hider, Zu Dong Liu, Anthony E. Theobald, Sarah Rose, Michelle Lockwood |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Denticity Tyrosine 3-Monooxygenase Pyridines Stereochemistry In Vitro Techniques Iron Chelating Agents Inhibitory postsynaptic potential Biochemistry Levodopa Structure-Activity Relationship Animals Chelation Enzyme Inhibitors Rats Wistar Pharmacology chemistry.chemical_classification Tyrosine hydroxylase biology Chemistry Ligand Brain Rats Enzyme Enzyme inhibitor Lipophilicity biology.protein |
| Zdroj: | Biochemical Pharmacology. 61:285-290 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/s0006-2952(00)00551-7 |
| Popis: | 1 3-Hydroxypyridin-4-ones are currently one of the main candidates for the development of orally active iron chelators. Small bidentate ligands tend to inhibit iron-containing metalloenzymes and therefore can cause undesirable side effects. A range of 3-hydroxypyridin-4-ones with different R 2 substitutents was selected for the investigation of the structure–activity relationship between the chemical nature of the ligand and the inhibition of mammalian tyrosine hydroxylase. Results indicated that lipophilicity was the dominant factor in controlling the ability of this class of chelator to inhibit mammalian tyrosine hydroxylase. Ligands with hydrophilic R 2 substitutents tended to be weak inhibitors. No significant correlation was found in this study between iron-binding affinity, extended R 2 chain length, and enzyme inhibitory activity. In contrast, both the LogP values of the entire molecule and of the R 2 segment correlated well with inhibitory activity. |
| Databáze: | OpenAIRE |
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