Effect of a new β-sitosterol analogue on plasma lipid concentrations in rats

Abstract

N-Substituted succinamic acid β-sitosteryl ester derivatives were prepared and evaluated. Compounds 1 and 2 were prepared in 76-92% yields by the reaction of β-sitosterol and succinic anhydride, followed by the activation of the resulting acid compound 1 by thionyl chloride or methyl chloroformate, and finally by amination with appropriate amines. Compound 2a (DANA87) was also easily obtained in one step by the direct addition of β-sitosterol to dicyclohexylcarbodiimide (DCC) in 80% yield. Administration of the dietary compound DANA87 resulted in significant decreases in total plasma cholesterol (TC) and low-density lipoprotein (LDL) cholesterol concentrations compared with controls in a rat model. High-density lipoprotein cholesterol and plasma triglyceride levels were not affected. These findings indicate that DANA87 functions as TC and LDL cholesterol-reducing agent. © 2004 Pharmaceutical Society of Japan.