Τίτλος:
Lipid-lowering (hetero)aromatic tetrahydro-1,4-oxazine derivatives with antioxidant and squalene synthase inhibitory activity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2008 American Chemical Society.
Συγγραφείς:
Kourounakis, A.P.
Charitos, C.
Rekka, E.A.
Kourounakis, P.N.
Περιοδικό:
Journal of Medicinal Chemistry
Λέξεις-κλειδιά:
2 [4 (2 fluorophenyl)phenyl] 4 methylmorpholinyl 2 ol; 2 [4 (4 chlorophenyl)phenyl] 4 methylmorpholinyl 2 ol; 2 [4 (4 fluorophenyl)phenyl] 4 methyloctahydro 1,4 benzoxazin 2 ol; 3 [4 (4 fluorophenyl)phenyl]octahydro 1,4 pyrido[2,1 c]oxazin 3 ol; antilipemic agent; aromatic compound; biphenyl derivative; cholesterol; low density lipoprotein cholesterol; morpholine derivative; oxazine derivative; squalene synthase; squalene synthase inhibitor; triacylglycerol; unclassified drug, animal experiment; animal model; animal tissue; antioxidant activity; article; controlled study; drug design; drug potency; drug synthesis; enzyme inhibition; hyperlipidemia; IC 50; in vivo study; lipid peroxidation; nonhuman; rat; structure activity relation, Animals; Antilipemic Agents; Antioxidants; Cholesterol; Enzyme Inhibitors; Farnesyl-Diphosphate Farnesyltransferase; Magnetic Resonance Spectroscopy; Microsomes, Liver; Morpholines; Rats; Triglycerides
