Anti-inflammatory and Hypolipidemic Effect of Novel Conjugates with Trolox and Other Antioxidant Acids

Objectives: A series of esters and amides, incorporating an antioxidant residue, such as trolox or caffeic acid, and various moieties with different biological activities, were synthesised. Results: The obtained compounds demonstrated considerable anti-inflammatory, radical scavenging and antioxidant action. Thus, they could reduce carrageenan-induced rat paw oedema by 31-60% at 150 mu mol/kg and inhibit rat microsomal membrane lipid peroxidation with IC50 values as low as 1.4 mu M which is much lower than that of trolox. Most of them could also inhibit soybean lipoxygenase. The thiomorpholine derivatives decreased significantly all lipidemic indices of Triton-induced hyper-lipidemia in rats. The most active, the caffeic acid derivative (6), decreases triglycerides, total cholesterol and low density lipoprotein, in the plasma of hyperlipidemic rats, by 70%, 67%, and 73%, respectively, at 150 mu mol/kg (i.p.). Conclusion: The synthesised compounds, designed to exhibit two or more pharmacological actions, may be considered useful in the study of agents addressed to conditions involving inflammation and oxidative stress.