Binding of phenothiazines to bovine serum albumin and related phenomena.

Abstract

The binding of 13 kinds of phenothiazines (PZS) to bovine serum albumin (BSA) was studied as a series of physico-chemical studies of an approach to an understanding of the membrane action of PZS. The data obtained were analyzed by the usual method for nonspecific binding of drug to protein reported by Klotz, et al. The results obtained by two equilibrium dialysis methods correlated well, and also there was found a correlation between equilibrium dialysis methods and gel filtration method. The binding increased with pH. The order of largeness of the effect of ion species was as follows : citrate>succinate>phosphate>acetate. The entropy change of binding was positive. The larger was the hydrophobicity of molecule of PZS with regard to structure, the more increased the amount bound to BSA. These results may suggest that a hydrophobic interaction takes part in the binding. The binding to BSA correlated with the surface activity of PZS, and also increased with the partition coefficient in dodecan/water system, as may suggest that a hydrophobic interaction plays an important role for the binding. There was found no correlation between the binding to BSA and the adsorbability by carbon black, contrary to the case of barbiturates previously reported. PZS of a similar chemical structure showed the correlations between the binding to BSA and the pharmacological activities, as might suggest that PZS of a similar chemical structure act on various interfaces and biological membranes in a similar way.