The antihyperlipidemic activities of 4(3H) quinazolinone and two halogenated derivatives in rats.
In the present study, the effects of subchronic treatments (4 weeks) of hypercholesterolemic (single) and diabetic-hypercholesterolemic (combined) rats with 4 (3H) quinazolinone and 2 halogenated derivatives (6, 8-dibromo-2-methy-4 (3H) quinazolinone and 6-iodo-2-methyl-4(3H) quinazolinone) at a sublethal dose level (2 mg/Kg) on cholesterol metabolism were investigated. Bezafibrate, a hypolipidemic drug was used as a reference compound for data comparison. Treatment of rats with single and combined hypercholesterolemia with quinazolinone compounds gave rise to highly significant reductions in serum total cholesterol and cholesterol ester levels, whereas serum triacylglycerol level was significantly reduced only after treatment with halogen-substituted quinazolinones in single hyper-cholesterolemia, compared to the control group. The effects of different quinazolinones and bezafibrate on reduction of serum LDL-C level were comparable in single hypercholesterolemia but significantly different in combined hypercholesterolemia. Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity.
Refaie
Fawzia M
FM
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. fawziarefaie@hotmail.com
Esmat
Amr Y
AY
Gawad
Soad M Abdel
SM
Ibrahim
Aida M
AM
Mohamed
Mona A
MA
D000818:Animals; D001629:Bezafibrate / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D052999:Quinazolinones; D051381:Rats
C510508:6,8-dibromo-2-methyl-4(3H)-quinazolinone; C510509:6-iodo-2-methyl-4(3H)-quinazolinone; D001786:Blood Glucose; D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D008055:Lipids; D011799:Quinazolines; D052999:Quinazolinones; D008315:Malondialdehyde; C061339:4-hydroxyquinazoline; D001629:Bezafibrate