Ferulic, Sinapic, 3,4-Dimethoxycinnamic Acid and Indomethacin Derivatives with Antioxidant, Anti-Inflammatory and Hypolipidemic Functionality

Abstract

A series of thiomorpholine and cinnamyl alcohol derivatives, conjugated with cinnamic acid-containing moieties, such as ferulic acid, sinapic acid and 3,4-dimethoxycinnamic acid, were synthesized and tested for their antioxidant, anti-inflammatory and hypolipidemic properties. An indomethacin ester with 2,6-di-tert-butyl-4-(hydroxymethyl)phenol was also prepared for reasons of comparison. The majority of the compounds demonstrated considerable antioxidant capacity and radical scavenging activity, reaching up to levels similar to the well-known antioxidant trolox. Some of them had an increased anti-inflammatory effect on the reduction of carrageenan-induced rat paw edema (range 17–72% at 150 μmol/kg), having comparable activity to the NSAIDs (non-steroidal anti-inflammatory drugs) used as reference. They had moderate activity in soybean lipoxygenase inhibition. All the tested compounds exhibited a significant decrease in lipidemic indices in Triton-induced hyperlipidemia in rats, whilst the most active triglycerides and total cholesterol decreased by 72.5% and 76%, respectively, at 150 μmol/kg (i.p.), slightly better than that of simvastatin, a well-known hypocholesterolemic drug, but with negligible triglyceride-lowering effect. Since our designed compounds seem to exhibit multiple pharmacological activities, they may be of use in occasions involving inflammation, oxidative stress, lipidemic deregulation and degenerative conditions.