Hydrophobic interactions of phenoxazine MDR modulators with bovine serum albumin

The binding of 10-[3'-(N-piperidino)propyl]-2-trifluoromethy]phenoxazine 1, 10- [3'-(beta -hydroxyethylpiperazino)propyl]-2-trifluoromethylphenoxazine 2, 10-[4'-(N-diethylamino)butyl]-2-trifluoromethylphenoxazine 3, 10-[4'-(N -piperidino)butyl]-2-trifluoromethylphenoxazine 4 and 10-[4'-(N-diethylamin o)butyl]-2-chlorophenoxazine 5 to bovine serum albumin (BSA) has been measu red by gel filtration and equilibrium dialysis methods. The binding of thes e modulators to albumin has been characterized by the following parameters: percentage of bound drug (beta), the association constant (K-I), the appar ent binding constant (k) and the free energy (DeltaF degrees). In addition, the displacing activity of hydroxyzine and acetylsalicylic acid on the bin ding of phenoxazine to albumin has been examined. The binding of phenoxazin e derivatives to serum transporter protein, BSA, is correlated with their p artition coefficients. The results of the displacing experiments reveal tha t the phenoxazine benzene rings and the tertiary amines attached to the sid e chain of the phenoxazine moiety are bound to a hydrophobic area on the al bumin molecule.