Hypocholesterolemic and hypolipidemic activity of some novel morpholine derivatives with antioxidant activity

In this investigation, we study the synthesis and the evaluation of antioxi dant and hypocholesterolemic activity of a number of 2-biphenylyl morpholin e derivatives, which are structurally similar to some substituted morpholin es possessing antioxidant activity, as well as to hypocholesterolemic 3-bia ryl-quinuclidines. The novel derivatives are found to inhibit the ferrous/a scorbate induced lipid peroxidation of microsomal membrane lipids, the most potent derivative, 2-(4-biphenyl)-4-methyl-octahydro-1,4-benzoxazin-2-ol ( compound 7), having an IC50 value of 250 mu M. In addition, these compounds demonstrate hypocholesterolemic and hypolipidemic action. The most active compound (7) decreases total cholesterol, low density lipoprotein, and trig lycerides in plasma of Triton WR-1339 induced hyperlipidemic rats by 54%, 5 1%, and 49%, respectively, at 28 mu mol/kg (ip). The above results indicate that the new molecules may be proven useful as leads for the design of nov el compounds as potentially antiatherogenic factors.