Solution properties of taurine and glycine conjugates of fusidic acid and its derivatives

Abstract

Taurine and glycine conjugates of fusidic acid, a steroid antibiotic previously shown to have structural and micellar properties similar to the bile salts (Carey, M.C. and Small D.M. (1971) J. Lipid Res. 12, 604–613), together with two fusidate analogues, have been characterized physicochemically. Both taurine and glycine conjugates of fusidic and 24,25-dihydrofusidic acids were shown to resemble the conjugated di-and trihydroxy bile salts in terms of their apparent pK values, aqueous solubilities, critical micellar concentrations, critical micellar temperatures and capacity to solubilize large amounts of lecithin and mixtures of lecithin and cholesterol. The conjugates of VD-795, a deacetoxy compound, were found to be insoluble in water at room temperature. Despite two α-oriented hydroxyl substituants, the conjugates of this fusidate derivative exhibited high critical micellar temperatures (“Krafft points”) comparable to the critical micellar temperatures of taurine and glycine conjugates of the monohydroxy bile salt, sodium lithocholate.