Interaction of substituted phenoxazine chemosensitizers with bovine serum albumin.

The binding of 10-[3'-[N-bis(hydroxyethyl)amino]propyl]phenoxazine [BPP], 10-[3'-[N-bis(hydroxyethyl)amino]propyl]-2-chlorophenoxazine [BPCP], 10-[3'-[N-bis-(hydroxyethyl)amino]propyl]-2-trifluoromethylphenoxazin e [BPFP], 10-(3'-N-pyrrolidino propyl)-2-chlorophenoxazine [PPCP] or 10-(3'-N-pyrrolidinopropyl)-2-trifluoromethylphenoxazine [PPFP] to bovine serum albumin (BSA) has been measured by gel filtration and equilibrium dialysis methods. The binding of these modulators to bovine serum albumin based on dialysis experiments has been characterized by the following parameters: percentage (beta) of bound drug, the association constant 'K1', the apparent binding constant 'k' and the free energy deltaFdegrees. The binding of phenoxazine derivatives to bovine serum albumin is correlated with their octanol-water partition coefficient, log10P. In addition, the displacing activity of hydroxyzine and acetylsalicylic acid on the binding of phenoxazines to albumin has been studied. The results of the displacing experiments showed 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.