Paper
Synthesis and hypolipidemic activity of 4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones in rodents.
Published Apr 1, 1993 · R. Simlot, R. Izydore, O. T. Wong
Journal of pharmaceutical sciences
23
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Abstract
A series of 4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones demonstrated potent activity in CF1 mice when administered intraperitoneally at 20 mg/kg/day, lowering both serum cholesterol and triglyceride levels significantly. The 4-(4-chlorophenyl)-substituted compounds demonstrated better hypolipidemic activity in rodents than 4-methoxy-, 4-nitro-, and 4-t-butylphenyl substitutions. Aryl and alkyl substitutions rather than benzoyl substitutions at position 4 demonstrated good hypocholesterolemic activity. Selected compounds were examined for the mode of action in rats in which serum cholesterol and triglyceride levels were reduced after administration of 20 mg/kg/day orally; tissue lipids were reduced after 14 days of administration, and bile and fecal lipids were increased by 44-250%. Serum lipoprotein levels were also modulated by the agents, with cholesterol levels in very low density lipoprotein and low density lipoprotein fractions being reduced by 2-57%. Cholesterol levels in the high density lipoprotein fraction were elevated by 94-341%. Activities of mouse hepatic enzymes were suppressed by the agents in a manner that suggested that the compounds interfere with de novo synthesis of lipids.
4-substituted 1-acyl-1,2,4-triazolidine-3,5-diones effectively lower serum cholesterol and triglyceride levels in rodents, suggesting their potential as a new class of cholesterol-lowering drugs.
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