Acetylacroninium salts as soluble prodrugs of the antineoplastic agent acronine.
The low aqueous solubility of acronine (approximately 2 mg/liter) has been overcome by identification of quaternary prodrug salts exhibiting apparent molar solubilities two to five orders of magnitude greater than acronine. The synthesis and kinetics of hydrolysis of the various prodrug acetylacroninium salts were studied, and the half-life for hydrolysis under conditions approximating the in vivo situation was estimated to be about 5 min. Such rapid reversion, together with the greatly increased solubility, appears to qualify the prodrug for intravenous use.
Acetylacroninium salts as soluble prodrugs of the antineoplastic agent acronine. The low aqueous solubility of acronine (approximately 2 mg/liter) has been overcome by identification of quaternary prodrug salts exhibiting apparent molar solubilities two to five orders of magnitude greater than acronine. The synthesis and kinetics of hydrolysis of the various prodrug acetylacroninium salts were studied, and the half-life for hydrolysis under conditions approximating the in vivo situation was estimated to be about 5 min. Such rapid reversion, together with the greatly increased solubility, appears to qualify the prodrug for intravenous use.