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Hydrophobic and ionic interactions of phenothiazine derivatives with bovine serum albumin

1972; Elsevier BV; Volume: 21; Issue: 7 Linguagem: Inglês

10.1016/0006-2952(72)90403-0

1873-2968

Josef Krieglstein, W. Meiler, Joachim Friedrich Staab,

Molecular spectroscopy and chirality

The binding of promethazine, trimeprazine, desmethylpromazine, desmethylchlorpromazine and perazine to bovine serum albumin was measured by sephadex gel filtration and equilibrium dialysis. The binding of these drugs to albumin is characterized by the following parameters: percentage (β) of bound drug, the association constant K1, the apparent binding constant k∗, and the free energy ΔF°. In addition, the displacing activity of hydroxyzine and acetylsalicylic acid on the binding of phenothiazines to albumin was examined. The binding of phenothiazine derivatives to bovine serum albumin is correlated with their octanol-water partition coefficients. The results allow the following interpretation of the phenothiazine-albumin complex. Only one of the phenothiazine benzene rings is attached to a hydrophobic area on the albumin molecule, while the basic dimethylamino group is associated with a negatively charged group on the protein surface. The aliphatic side chain obviously does not directly take part in binding. But a methyl group in the aliphatic chain as in the case of promethazine or trimeprazine enhances the binding of the molecule significantly.