Design, synthesis and evaluation of antihyperlipidemic agents combining antioxidant and antiinflammatory activity
Alexios N. Matralis, Angeliki P. Kourounakis · 2013
Atherosclerosis is a multifactorial disease in need of pharmaceutical treatment that can address a multiplicity of targets. We hereby describe the synthesis and evaluation of compounds in which antioxidant, anti-inflammatory as well as squalene synthase (SQS) inhibitory activities are combined by design, in a series of simple molecules, extending their potential activity against atherosclerosis. The activity of the synthesized antihyperlipidemic morpholine derivatives, in which we combined several pharmacophore moieties, was evaluated in vitro for antioxidant, inhibition of SQS and lipoxygenase activity as well as in vivo for antihyperlipidemic and anti-inflammatory effects. Most compounds had promising activity while structure-activity relationships are discussed. These results, taken together, show a promising alternative and novel approach for the design and development of antiatherosclerosis agents.