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We investigated the effects of T-2591, a new ureidophenol derivative, on low density lipoprotein (LDL) oxidation, acyl CoA: cholesterol acyltransferase (ACAT) and foam cell formation of macrophages in vitro. T-2591 inhibited both copper ion--and endothelial cell--induced LDL oxidation with higher potencies than probucol did. It inhibited ACAT from rabbit intestine, liver and aorta, the respective IC50 values being 0.26, 4.6 and 4.1 microM. It also inhibited ACAT from the mouse macrophage cell line J774 A.1, and its IC50 value (0.067 microM) was much lower than that of CI-976 (4.1 microM). This probably accounts for the inhibition of foam cell formation measured as cholesteryl ester formation in both mouse peritoneal macrophages and J774 A.1 cells at low concentrations (IC50; 0.06 and 0.44 microM, respectively). These observations suggest that T-2591 should be evaluated as a potential tool to retard atherosclerosis in animal models.

Inhibitory Effect of a New Ureidophenol Derivative T-2591 on LDL Oxidation and ACAT Activity.