Abstract
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 microM) as well as rat squalene synthase (IC50 for most between 1-10 microM). 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 micromol/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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antioxidants / chemistry
-
Antioxidants / pharmacology*
-
Cholesterol / blood
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology*
-
Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors*
-
Hypolipidemic Agents / chemistry
-
Hypolipidemic Agents / pharmacology*
-
Magnetic Resonance Spectroscopy
-
Microsomes, Liver / drug effects
-
Microsomes, Liver / enzymology
-
Morpholines / chemistry
-
Morpholines / pharmacology*
-
Rats
-
Triglycerides / blood
Substances
-
Antioxidants
-
Enzyme Inhibitors
-
Hypolipidemic Agents
-
Morpholines
-
Triglycerides
-
Cholesterol
-
Farnesyl-Diphosphate Farnesyltransferase