Binding of Spirolactones to Human Plasma Proteins
| Autor: | L.M. Hofmann, Yie W. Chien, L.C. Tao, Howard J. Lambert |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
chemistry.chemical_classification
Binding Sites biology Chemistry Stereochemistry Serum albumin Pharmaceutical Science Spironolactone Binding constant Protein–protein interaction Structure-Activity Relationship Hydrolysis Lipophilicity biology.protein Binding site Serum Albumin Equilibrium constant Lactone Protein Binding |
| Zdroj: | Journal of Pharmaceutical Sciences. 65:1337-1340 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.2600650919 |
| Popis: | The lipophilicity and plasma binding of 16 spirolactones and 4 hydroxy acid analogs were determined. Mathematical expressions were derived to correlate quantitatively the extent of plasma binding to the lipophilicity of the drugs. The nonspecific binding of these spirolactones and their hydroxy acid analogs was also analyzed using purified serum albumin. A computer program was developed to examine the mechanism of drug‐serum protein interactions. One class of binding sites was observed for the range of concentrations used. The number of binding sites and the equilibrium binding constant were computed and were sensitive to substitution at the C‐6 and C‐7 positions. Hydrolysis of the C‐17 lactone ring in spirolactones to form hydroxy acid analogs resulted in a decrease in the lipophilicity and, hence, the equilibrium constant for binding. |
| Databáze: | OpenAIRE |
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