Thiourea and benzamide compounds, composition and methods of treating or preventing inflammatory diseases and atherosclerosis

Abstract

The authors have synthesised a series of thiourea and benzamide compounds and claim their use as potential anti-inflammatory and/or anti-atherosclerotic drugs. 280 Compounds were synthesised and tested for lipoxygenase (LO) inhibitory activity in an in vitro assay system using the purified rabbit reticulocyte 15-LO. Some of them were shown to be potent LO inhibitors with IC₅₀ values as low as 2 nM. In an in vitro model of inflammation, several compounds inhibited monocyte recruitment with an EC₅₀ in the lower μM-range and some inhibitors slowed down the development of atherosclerotic lesions in an animal atherosclerosis model. However, there was no correlation between LO inhibition and anti-atherogenic or anti-inflammatory activity.

• eicosanoids
• inflammation
• low density lipoprotein
• oxidative stress