Interaction of substituted phenoxazine chemosensitizers with bovine serum albumin

The binding of 10-[3'-[N-bis(hydroxyethyl)amino]propyl]phenoxazine [BPP], 1 0-[3'-[N-bis(hydroxyethyl)amino]propyl]-2-chlorophenoxazine [BPCP], 10-[3'- [N-bis-(hydroxyethyl)amino]propyl]-2-trifluoromethylphenoxazine [BPFP], 10- (3'-N-pyrrolidino propyl)-2-chlorophenoxazine [PPCP] or 10-(3'-N-pyrrolidin opropyl)-2-trifluoromethylphenoxazine [PPFP] to bovine serum albumin (BSA) has been measured by gel filtration and equilibrium dialysis methods. The b inding of these modulators to bovine serum albumin based on dialysis experi ments has been characterized by the following parameters: percentage (beta) of bound drug, the association constant 'K-1', the apparent binding consta nt 'k' and the free energy Delta F degrees. The binding of phenoxazine deri vatives to bovine serum albumin is correlated with their octanol-water part ition coefficient, log(10) P. In addition, the displacing activity of hydro xyzine and acetylsalicylic acid on the binding of phenoxazines to albumin h as been studied. The results of the displacing experiments showed that the phenoxazine benzene rings and the tertiary amines attached to the side chai n of the phenoxazine moiety are bound to a hydrophobic area on the albumin molecule. (C) 1999 Elsevier Science B.V. All rights reserved.