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Hypolipidemic activity of 6‐alkoxycarbonyl‐3‐aryl‐1,3,5‐triazabicyclo[3.1.0]hexane‐2,4‐diones and 2‐alkoxycarbonyl‐5‐aryl‐1,3,5‐triazine‐4,6(1H,5H)‐diones in rodents
Author(s) -
Izydore Robert A.,
Wong O. T.,
Hall Iris H.
Publication year - 1993
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536643
Subject(s) - very low density lipoprotein , chemistry , cholesterol , triglyceride , sterol o acyltransferase , acyl coa , medicine , acyltransferase , endocrinology , lipoprotein , biochemistry , enzyme , biology
Significant hypolipidemic activity was demonstrated by 6‐ethoxycarbonyl‐3‐phenyl‐1,3,5‐triazabicyclo[3.1.0]hexane‐2,4‐dione, 2‐ethoxycarbonyl‐5‐phenyl‐1,3,5‐triazine‐4,6(1H,5H)‐dione and 2‐ethoxycarbonyl‐5‐(4‐chlorophenyl)‐1,3,5‐trizine‐4,6(1H,5H)‐dione in rodents at 20 mg/kg/day. These agents lowered serum cholesterol and triglyceride levels by approximately 40% in mice after 16 d. Tissue lipids in rat liver, small intestinal mucosa, aortic wall and feces were reduced by treatment with the agents. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol levels were reduced in the rat; high density lipoprotein (HDL) cholesterol levels were elevated after 14 d of treatment. The activities of regulatory enzymes, e.g. , acetyl‐CoA synthetase, acyl‐CoA:cholesterol acyltransferase, cholesterol 7α‐hydroxylase, sn ‐glycerol‐3‐phosphate acyltransferase, phosphatidylate phosphohydrolase and heparin‐induced lipoprotein lipase, involved in de novo synthesis of hepatic lipids were affected by the agents. The new compounds may represent another class of potentially useful hypolipidemic agents for the treatment of atherosclerosis since HDL cholesterol levels were increased and VLDL and LDL cholesterol levels were lowered by some of the agents.