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Lipid-Lowering (Hetero)Aromatic Tetrahydro-1,4-Oxazine Derivatives with Antioxidant and Squalene Synthase Inhibitory Activity

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journal contribution
posted on 25.09.2008, 00:00 by Angeliki P. Kourounakis, Christos Charitos, Eleni A. Rekka, Panos N. Kourounakis
A number of newly synthesized 2-[4-(hetero)aromatic]phenyl-2-hydroxy-tetrahydro-1,4-oxazine derivatives were found to inhibit lipid peroxidation (IC50 of the most potent was 20 μM) as well as rat squalene synthase (IC50 for most between 1−10 μM). Antidyslipidemic action was demonstrated in vivo: the most active compound decreased triglycerides, total cholesterol, and LDL-cholesterol of hyperlipidemic rats by 64, 67, and 82%, respectively, at 56 μmol/kg (ip). Most of the novel compounds are more active than the structurally related and reference biphenyl-morpholine, pointing to useful structural approaches for the design of antiatherosclerotic agents.

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