The hypolipidemic activity of 1-N-3-methylphthalimido-butan-3-semicarbazone in rodents.
1-N-(3-Methylphthalimido)butan-3-one semicarbazone demonstrated potent hypolipidemic activity normal rats and mice and hyperlipidemic diet-induced mice. The compound decreased tissue lip levels and increased the fecal excretion of cholesterol and triglycerides. After 2 weeks of administration, serum lipoprotein levels were modulated so that very low-density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol concentrations were reduced and high-density lipoproteins (HDL) cholesterol concentrations were elevated to levels unprecedented by the cyclic imide derivatives previously tested. The VLDL triglyceride content was also reduced. Hepatic in vitro enzymatic studies demonstrated that the compound suppressed the activity of enzymes in the early synthesis of fatty acids and cholesterol and the regulatory enzymes for the de novo synthesis of triglycerides.
Wong
O T
OT
Division of Medicinal Chemistry & Natural Products, School of Pharmacy, University of North Chapel Hill 27599.
Hall
I H
IH
Chapman
J M
JM
D000818:Animals; D001011:Aorta / Q000032:analysis / Q000187:drug effects; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D005243:Feces / Q000032:analysis; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000032:analysis / Q000187:drug effects; D008055:Lipids / Q000032:analysis / Q000097:blood; D008099:Liver / Q000032:analysis / Q000187:drug effects; D008297:Male; D051379:Mice; D010797:Phthalimides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012664:Semicarbazones / Q000494:pharmacology*; D014280:Triglycerides / Q000032:analysis / Q000097:blood
D000960:Hypolipidemic Agents; D008055:Lipids; D010797:Phthalimides; D012664:Semicarbazones; D014280:Triglycerides; C059857:1-N-3-methylphthalimidobutan-3-semicarbazone; D002784:Cholesterol