Hydrophobic interactions of phenoxazine MDR modulators with bovine serum albumin

The binding of 10-[3'-(N-piperidino)propyl]-2-trifluoromethylphenoxazine 1, 10-[3'-(β-hydroxyethylpiperazino)propyl]-2-trifluoromethylph enoxazine 2, 10-[4'-(N-diethylamino)butyl]-2-trifluoromethylphenoxazine 3, 10-[4'-(N-piperidino)butyl]-2-trifluoromethylphenoxazine 4 and 10-[4'-(N-diethylamino)butyl]-2-chlorophenoxazíne 5 to bovine serum albumin (BSA) has been measured by gel filtration and equilibrium dialysis methods. The binding of these modulators to albumin has been characterized by the following parameters: percentage of bound drug (β), the association constant (K₁), the apparent binding constant (k) and the free energy (AF°). In addition, the displacing activity of hydroxyzine and acetylsalicylic acid on the binding of phenoxazine to albumin has been examined. The binding of phenoxazine derivatives to serum transporter protein, BSA, is correlated with their partition coefficients. The results of the displacing experiments reveal that the phenoxazine benzene rings and the tertiary amines attached to the side chain of the phenoxazine moiety are bound to a hydrophobic area on the albumin molecule.